Device and method for sustained release of low water solubility therapeutic agent in solubilizer

ABSTRACT

Devices and methods for administering a therapeutic agent, comprising an implantable delivery device. Exemplary embodiments comprise a reservoir in fluid communication with a channeled member, and a compound comprising the therapeutic agent and a solubilizer disposed within the reservoir.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Patent ApplicationSer. No. 61/864,768, filed Aug. 12, 2013, the contents of which areincorporated by reference herein.

BACKGROUND INFORMATION

Therapeutic agent (e.g. drug) delivery is an important aspect of medicaltreatment since the efficacy of a drug is directly related to itsadministration. Some therapies require repetitive drug administration tothe patient over a long period of time, and in many cases long termconsistent administration of drug is desirable. In addition, patientcompliance with repetitive, long term drug administration can be anissue in some instances.

Considerable advances have been made in the field of drug deliverytechnology over the last three decades, resulting in many breakthroughsin clinical medicine. The creation of therapeutic agent delivery devicesthat are capable of delivering therapeutic agents in controlled waysstill presents many challenges. One of the significant requirements foran implantable drug delivery device is controlled release of therapeuticagents, ranging from small drug molecules to larger biologicalmolecules. In many instances, it is particularly desirable to achieve acontinuous drug release profile whereby the concentration of drug in thebloodstream remains substantially constant throughout an extendeddelivery period. It can also be desirable for the implantable drugdelivery device to provide continuous drug release via passive controlmechanisms to minimize device complexity.

These devices have the potential to improve therapeutic efficacy,diminish life-threatening side effects, improve patient compliance,minimize the intervention of healthcare personnel, reduce the durationof hospital stays, and decrease the diversion and abuse of controlledsubstances.

By providing a more consistent release, it is possible to improve thetherapeutic efficacy and simultaneously decrease the side effects (e.g.toxicity of temporary overdosing or diminished activity associated witha small drug concentration in the plasma) associated with multipleadministrations of higher dosages.

The solubility of certain therapeutic agents can provide dosing andapplication challenges. For example, a therapeutic agent with poor watersolubility requires a greater volume of solvent to dissolve thetherapeutic agent in the injection or implantable delivery device inorder to provide an effective dosing level for extended duration. Incases where it is desirable to have an extended dosing period, thevolume of solvent and the dissolved therapeutic agent may be large, andtherefore the implantable delivery device may be prohibitively large.Long term dosing of low solubility therapeutic agents in a smallimplantable delivery device is desirable.

In certain applications, implantable drug delivery devices mayincorporate geometric constraints to provide for a controlled releaserate of the therapeutic agent. For example, certain implantable drugdelivery devices may utilize nanochannels to restrict the rate at whichtherapeutic molecules can diffuse from the device. In particularapplications, geometric constraints can control the diffusion rate sothat it is substantially independent of the concentration of theremaining therapeutic agent within the delivery device. These geometricconstraints include nanochannels that are fabricated 2-5 times largerthan the hydrodynamic size of the agent molecule. However, if thetherapeutic molecule is sufficiently small, it can be difficult, if notimpossible, to create a geometric constraint dimensioned to provide fora controlled release rate at a therapeutically-effective level. Inaddition, such small geometric constraints may lead to insufficientrelease of the agent.

The issues raised above are merely exemplary of the potentialshortcomings of existing systems and are not intended to be anexhaustive listing of the issues addressed by embodiments of the presentdisclosure.

SUMMARY

Devices have recently been developed to address some of the issuesdescribed above. However, it was until recently believed that theenvironment within an implantable device should approximate thesurrounding physiologic environment outside the device in order tofacilitate administration of a therapeutic agent from the device. Forexample, previous efforts for therapeutic agent administration attemptedto match the saline concentration of fluid inside the device to that ofthe outside environment in order to minimize boundary layers between thetwo environments and promote molecular diffusion of the therapeuticagents from the implantable device to the outside environment.

Recent efforts have discovered that in certain instances solubilizerswithin the device that do not approximate the surrounding environmentcan be successfully utilized. For example, certain oils have been foundto effectively solubilize testosterone and testosterone esters toprovide effective testosterone replacement therapy. It was previouslybelieved that many oils would be effective at solubilizing therapeuticagents (including testosterone), but would not be effective atdelivering the therapeutic agents to the patient. It is well known thatoils are not miscible with water. This surprising result contradictedprevailing scientific understanding and literature publications whichheld that the boundary layer between the oil and saline environmentwould restrict or prevent a therapeutic agent from being effectivelyadministered.

Exemplary embodiments of the present invention, however, utilize atherapeutic agent dissolved in a solubilizer that has relatively lowmiscibility with the outside environment in a reservoir of an implantthat comprises channels to assist in controlling the release rate of thedissolved therapeutic agent. In particular embodiments, the implant maycomprise nanochannels and/or microchannels.

In particular embodiments, the solubilizer may comprise one or more ofthe following: Gelucire 44/14, Gelucire 50/13, Peceol, Labrafil M2125CS, Labrafil M1944 CS, Labrasol, Tween 80, Crodasol, Brij 30, Glycerox767, NOVOL (Oleyl Alcohol), ETOCAS (PEG-35 Castor Oil), Arlosolve(Dimethyl lsosobride), PEG300, Maisine 35-1, Transcutol HP, Glycerin,Span 80, Span 85, Compritol 888, Propylene Glycol, Dibutyl Sebacate,Triacetin, Miglyol 810, Miglyol 812, Myvacet, Softigen 701, Softigen767, Kolliphor HS15, Kolliphor RH40, Kolliphor ELP, Stearic Acid, CetylPalmitate, Lauroglycol 90, Lauroglycol FCC, Labrafac PG, LabrafacLipophile WL 1349, Miranol, Soybean Oil, Corn Oil, Olive Oil, CastorOil, Sesame Oil, Light Mineral Oil, Heavy Mineral Oil, Coconut Oil,Canola Oil, Dimethyl Sulfoxide (DMSO), N-Methylpyrrolidone (NMP), BenzylBenzoate, Capryol 90, Capryol PGMC, Glyceryl Monostearate, Vitamin ETPGS and Benzyl Alcohol. This list is exemplary, and other appropriatesolubilizers, cationic, anionic and nonionic surfactants, fatty acidesters, fatty acid alcohols, and other substances singularly or incombination known to those skilled in the art to enhance the aqueoussolubility or provide for highly concentrated, low water miscibilitysuspensions of a target therapeutic agent within the device may be used.In specific embodiments, the solubilizer may be non-aqueous.

The inclusion of a concentrated therapeutic agent dissolved in asolubilizer within the reservoir can address several issues noted inexisting systems. For example, portions of the solubilizer (with thedissolved therapeutic agent) that are small enough to pass through thechannels can separate over time and be released to provide a more steadyconcentration of therapeutic agent. By providing a more steadyconcentration, rather than a concentration that is initially high andsubsequently reduced (as might be the case for therapeutic agentdelivery outside the constrained reservoir), the geometry of thedelivery device can be optimized. For example, it may be possible toincrease the size of the channels because the concentration of thereservoir is maintained at a more steady level by the presence of thenon-miscible therapeutic agent, so less geometric constraint isrequired. Also, one or more dimensions of the portions of thesolubilizer (with the dissolved therapeutic agent) that break away canbe tens or hundreds of nanometers, so that channeled members withgeometrics constraints, e.g., nanochannels having dimensions the sizerange 50 to 250 nanometers, can regulate the release of these portions.

The use of a therapeutic agent dissolved in a solubilizer may also makeit possible to administer therapeutic agents that would otherwise bedifficult to administer consistently at therapeutic levels with avariable-concentration reservoir and a channeled member.

Exemplary embodiments of the present disclosure comprise an implantabledevice comprising a reservoir, a channeled member in fluid communicationwith the reservoir; and a compound comprising a therapeutic agent and asolubilizer disposed within the reservoir and in fluid communicationwith the channeled member.

Certain embodiments may include a device for administering a therapeuticagent, where the device comprises: an implantable device comprising areservoir; a channeled member in fluid communication with the reservoir;and a compound comprising the therapeutic agent and a solubilizerdisposed within the reservoir and in fluid communication with thechanneled member.

In specific embodiments the compound may comprise testosterone or atestosterone ether, ester, or salt. In particular embodiments, thecompound may comprise testosterone enanthate, testosterone cypionate,testosterone propionate, testosterone decanoate, and/ormethyltestosterone. In certain embodiments, the solubilizer may comprisean oil. In particular embodiments, the solubilizer may be non-aqueous.

In specific embodiments, the solubilizer may comprise at least one of:Gelucire 44/14, Gelucire 50/13, Peceol, Labrafil M2125 CS, LabrafilM1944 CS, Labrasol, Tween 80, Crodasol, Brij 30, Glycerox 767, NOVOL(Oleyl Alcohol), ETOCAS (PEG-35 Castor Oil), Arlosolve (Dimethyllsosobride), PEG300, Maisine 35-1, Transcutol HP, Glycerin, Span 80,Span 85, Compritol 888, Propylene Glycol, Dibutyl Sebacate, Triacetin,Miglyol 810, Miglyol 812, Myvacet, Softigen 701, Softigen 767, KolliphorHS15, Kolliphor RH40, Kolliphor ELP, Stearic Acid, Cetyl Palmitate,Lauroglycol 90, Lauroglycol FCC, Labrafac PG, Labrafac Lipophile WL1349, Miranol, soybean oil, corn oil, olive oil, castor oil, sesame oil,light mineral oil, heavy mineral oil, coconut oil, canola oil, dimethylsulfoxide (DMSO), N-Methylpyrrolidone (NMP), Benzyl Benzoate, CapryolPGMC, Glyceryl Monostearate, Vitamin E TPGS and Benzyl Alcohol.

In certain embodiments, the channeled member may comprise a nanochannel.In specific embodiments, the nanochannel may have a dimension of up to50 nm, or have a dimension in the range of 50-100 nm; 100-150 nm;150-170 nm; 170-190 nm; 190-210 nm; 210-225 nm; 225-240 nm; or 240-250nm. In particular embodiments, the channeled member may comprisemicrochannels. In certain embodiments, the device may comprise aninjection port and/or a vent.

Specific embodiments include a method of administering a therapeuticagent, where the method may comprise: inserting a device as disclosedherein into an area of a human or animal anatomy (where the devicecomprises: a reservoir; a channeled member in fluid communication withthe reservoir; and a compound comprising the therapeutic agent and asolubilizer disposed within the reservoir and in fluid communicationwith the channeled member); and releasing at least a portion of thetherapeutic agent from the device into the area of the human or animalanatomy.

In certain embodiments of the method, the device may be configured torelease the therapeutic agent at a substantially constant release ratefor a dosage period of at least one week, of at least one month, of atleast six months, or of at least one year.

In specific embodiments of the method, the compound may comprisetestosterone or a testosterone ether, ester, or salt. In particularembodiments of the method, the compound may comprise testosteroneenanthate, testosterone cypionate, testosterone propionate, testosteronedecanoate, and/or methyltestosterone. In certain embodiments of themethod, solubilizer may comprise an oil. In particular embodiments ofthe method, the solubilizer may be non-aqueous.

In specific embodiments of the method, the solubilizer may comprise atleast one of: Gelucire 44/14, Gelucire 50/13, Peceol, Labrafil M2125 CS,Labrafil M1944 CS, Labrasol, Tween 80, Crodasol, Brij 30, Glycerox 767,NOVOL (Oleyl Alcohol), ETOCAS (PEG-35 Castor Oil), Arlosolve (Dimethyllsosobride), PEG300, Maisine 35-1, Transcutol HP, Glycerin, Span 80,Span 85, Compritol 888, Propylene Glycol, Dibutyl Sebacate, Triacetin,Miglyol 810, Miglyol 812, Myvacet, Softigen 701, Softigen 767, KolliphorHS15, Kolliphor RH40, Kolliphor ELP, Stearic Acid, Cetyl Palmitate,Lauroglycol 90, Lauroglycol FCC, Labrafac PG, Labrafac Lipophile WL1349, Miranol, soybean oil, corn oil, olive oil, castor oil, sesame oil,light mineral oil, heavy mineral oil, coconut oil, canola oil, dimethylsulfoxide (DMSO), N-Methylpyrrolidone (NMP), Benzyl Benzoate, CapryolPGMC, Glyceryl Monostearate, Vitamin E TPGS and Benzyl Alcohol.

In certain embodiments of the method, the channeled member may comprisea nanochannel. In specific embodiments, the nanochannel may have adimension of up to 50 nm, or have a dimension in the range of 50-100 nm;100-150 nm; 150-170 nm; 170-190 nm; 190-210 nm; 210-225 nm; 225-240 nm;or 240-250 nm. In particular embodiments of the method, the channeledmember may comprise microchannels. In certain embodiments of the method,the device may comprise an injection port and/or a vent.

In the following, the term “coupled” is defined as connected, althoughnot necessarily directly, and not necessarily mechanically.

The use of the word “a” or “an” when used in conjunction with the term“comprising” in the claims and/or the specification may mean “one,” butit is also consistent with the meaning of “one or more” or “at leastone.” The term “about” means, in general, the stated value plus or minus10%. The use of the term “or” in the claims is used to mean “and/or”unless explicitly indicated to refer to alternatives only or thealternative are mutually exclusive, although the disclosure supports adefinition that refers to only alternatives and “and/or.”

The terms “comprise” (and any form of comprise, such as “comprises” and“comprising”), “have” (and any form of have, such as “has” and“having”), “include” (and any form of include, such as “includes” and“including”) and “contain” (and any form of contain, such as “contains”and “containing”) are open-ended linking verbs. As a result, a method ordevice that “comprises,” “has,” “includes” or “contains” one or moresteps or elements, possesses those one or more steps or elements, but isnot limited to possessing only those one or more elements. Likewise, astep of a method or an element of a device that “comprises,” “has,”“includes” or “contains” one or more features, possesses those one ormore features, but is not limited to possessing only those one or morefeatures. Furthermore, a device or structure that is configured in acertain way is configured in at least that way, but may also beconfigured in ways that are not listed.

The term “channeled member” as used herein includes structurescomprising microchannels and/or nanochannels, including not limited to,any of the exemplary nanochannel devices disclosed in U.S. patentapplication Ser. No. 12/618,233 filed Nov. 13, 2009 (U.S. PatentPublication 20100152699) and entitled “Nanochanneled Device and RelatedMethods” and International Patent Application Number PCT/US10/30937(WIPO Patent Publication WO/2011/146699) filed Apr. 13, 2010 andentitled “Nanochanneled Device and Method of Use”, both of which areincorporated herein by reference.

The term “microchannel” is defined as a channel with a cross-sectionhaving at least one dimension (e.g. height, width, diameter, etc.) thatis greater than 500 nm and less than 50 μm.

The term “nanochannel” is defined as a channel with a cross-sectionhaving at least one dimension (e.g. height, width, diameter, etc.) thatis less than 500 nm.

Other objects, features and advantages of the present invention willbecome apparent from the following detailed description. It should beunderstood, however, that the detailed description and the specificexamples, while indicating specific embodiments of the invention, aregiven by way of illustration only, since various changes andmodifications within the spirit and scope of the invention will beapparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1 is a graph that illustrates a plasma drug concentration over timewhen the drug is administered via traditional intravenous (IV) methods.

FIG. 2 is a graph that illustrates a plasma drug concentration over timewhen the drug is administered via a therapeutic agent and solubilizer inan implantable delivery device.

FIG. 3 is a top perspective view of an implantable delivery device.

FIG. 4 is a bottom perspective view of an implantable delivery device.

FIG. 5 is a section view of the embodiment of FIG. 3.

FIG. 6 is a scanning electron microscope (SEM) cross-section image of aportion of a channeled member of FIG. 3.

FIG. 7 is a scanning electron microscope (SEM) cross-section image of aportion of a channeled member of FIG. 3.

FIG. 8 is a graph of a cumulative release rate of testosterone enanthate(TE) from a channeled member in combination with sesame oil andLabrasol.

FIG. 9 is a graph of a cumulative release rate of testosterone enanthate(TE) from a channeled member in combination with sesame oil.

FIG. 10 is a graph of a cumulative release rate of testosteroneenanthate (TE) from a channeled member in combination with Vitamin ETPGS.

FIG. 11 is a graph of a cumulative release rate of testosteroneenanthate (TE) from a channeled member in combination with sesame oiland benzyl alcohol.

FIG. 12 is a graph of a cumulative release rate of testosteroneenanthate (TE) from a channeled member.

FIGS. 13-21 are graphs of a cumulative release rate of testosteroneenanthate (TE) from a channeled member of with nanochannel heights of160 nm, 190 nm, 200 nm, 210 nm, 220 nm, and 250 nm, and with and withouta hydrophilic surface treatment included.

FIG. 22 is a graph of a concentration of testosterone serum in vivo.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

As previously mentioned, a more constant drug administration can providenumerous advantages over periodic administrations that are initiallyabove the therapeutic range and subsequently diminish to below thetherapeutic range. Referring to FIG. 1, a graph illustrates plasma drugconcentration versus time in one example of a typical conventional drugadministration utilizing period dosage. As illustrated in FIG. 1, thedrug concentration is initially significantly above the therapeuticrange and subsequently reduces to a level below the therapeutic range.When the concentration is reduced to a level below the therapeuticrange, another dosage can be administered and the drug concentrationagain exceeds the therapeutic range before being reduced into thedesired therapeutic range.

FIG. 2 shows the plasma drug concentration (PDC) over time when the drugis administered via a solid matter therapeutic agent in an implantabledelivery device, as described in more detail below. The employment of asolid matter therapeutic agent in an implantable delivery device forconstant drug release can improve the efficacy of the treatment. Inaddition it can avoid frequent injections and, in many cases, reduce orsolve the issues of patient compliance.

Referring now to FIGS. 3-5, an implantable delivery device (IDD) 100 isshown in perspective views (FIGS. 3 and 4) and a sectional view (FIG.5). It is understood that the figures shown are not to scale and areintended for representative purposes only. In this embodiment, IDD 100comprises a reservoir 110 with a channeled member 130. In the exemplaryembodiment shown, IDD 100 also comprises an injection port 140, a vent145 and exit ports 150. In particular embodiments, the injection port140 and vent port 145 are filled with a substance, for example, siliconerubber, and the channeled member 130 is in fluid communication with theexit ports 150. In particular embodiments, IDD 100 may be formed fromsuitable bio-compatible materials including for example Polyether etherketone (PEEK) or titanium.

In particular embodiments, channeled member 130 may comprisemicrochannels, and in specific embodiments, channeled member 130 maycomprise nanochannels. Channeled member 130 may also comprise bothmicrochannels and nanochannels in certain embodiments. In someembodiments, channeled member 130 may be an integral component of IDD100, while in other embodiments, channeled member 130 may be a separatecomponent that is coupled to or inserted into IDD 100. In particularembodiments, channeled member 130 may have a surface area of less than 1cm² exposed to reservoir 110, and in specific embodiments may comprise asurface area of approximately 0.75 cm² exposed to reservoir 110. Incertain embodiments, channeled member 130 may be approximately 6 mm×6mm.

In particular embodiments, channeled member 130 may be equivalent to thenanochannel delivery device (and may be constructed via the associatedmethods) disclosed within in U.S. Patent Publication 20100152699,incorporated herein by reference. In other embodiments, channeled member130 may comprise microchannels without nanochannels. In certainembodiments, channeled member 130 may comprise one or more coatingscompatible with in vivo use, including for example, coating as describedin U.S. Patent Publication 20110288497. Referring now to FIGS. 6 and 7,scanning electron microscope (SEM) images of a portion of a channeledmember are shown after in vivo testing without a coating (FIG. 6) andwith a coating (FIG. 7).

In exemplary embodiments, reservoir 110 can be filled with an activepharmaceutical ingredient (API) 200 dissolved in a solubilizer 210. Inparticular embodiments, API 200 may comprise, for example, testosteroneor a testosterone ester and solubilizer 210 may comprise one or more ofthe compounds listed above in the Summary section of this disclosure.

During use, IDD 100 can be used to administer API 200 by inserting IDD100 into an area of a human anatomy, including for example,subcutaneously. With IDD 100 inserted into the desired anatomical area,portions of solubilizer 210 (with dissolved API 200) that are smallenough to pass through channeled member 130 can be released over timeinto the area of the human anatomy or for systemic circulation. Incertain embodiments, the solubility enhancement of API 200 andsolubilizer 210 can range from approximately 2×, 3×, 4×, 5×, 6×, 7×, 8×,9×, 10×, 11×, 12×, 13×, 14×, 15×, 16×, 17×, 18×, 19×, 20×, 21×, 22×,23×, 24×, 25×, 26×, 27×, 28×, 29×, 30× or higher. In particularembodiments, the solubility enhancement can be up to 1000× and higher.For example, with testosterone the native water solubility is 35 μg/ml,but in ethanol it is approximately 750 mg/ml, which is a 20,000×increase.

In certain embodiments, IDD 100 and channeled member 130 can beconfigured to release up to approximately 3, 4, 5, 6, 7, 8, 9 or 10 mgof API 200 per day over a period of time up 12 months. In otherembodiments, IDD 100 may be configured to release a different dosageover shorter or longer periods of time. For example, in particularembodiments IDD 100 can be configured to release 0.1, 0.2, 0.3, 0.4,0.5, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8,1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8 or 2.9 mg/day of API200. IDD 100 can also be configured to release API 200 over a matter of1, 3, 4, 5, 6, or 7 days, 1, 2, 3, or 4 weeks, or 1, 2, 3, 4, 5, 6, 7,8, 9, 10, 11, 12 months. In certain exemplary embodiments, IDD 100 canbe configured to release between approximately 1 gm and 2 gm of API 200over a period of approximately 12 months. In particular embodiments, IDD100 and channeled member 130 can be configured to release betweenapproximately 200-700 μg/day/cm² (as measured at the surface area of thechanneled member exposed to reservoir 110).

In particular embodiments, therapeutic agent may comprise one or more ofthe following substances: testosterone, testosterone esters (includingbut not limited to testosterone enanthate, testosterone cypionate,testosterone propionate, and methyltestosterone). Many other therapeuticagents and other substances known to have low solubility in water may beused in the manner of this disclosure.

FIGS. 6 and 7 show an SEM cross-section image of a portion of achanneled member, including microchannels in fluid communication withnanochannels of height 200 nm and 50 nm, respectively.

FIG. 8 is a graph of a cumulative release rate of testosterone enanthate(TE) from a channeled member in combination with sesame oil and Labrasolin an 8:1:1 ratio of TE/sesame oil/Labrosol. FIG. 9 is a graph of acumulative release rate of TE and sesame oil in a 9:1 ratio, while FIG.10 is a graph of TE and Vitamin E TPGS in a 9:1 ratio. FIG. 11 is agraph of a cumulative release rate of TE/sesame oil/benzyl alcohol in an8:1:1 ratio. FIG. 12 is a graph of a cumulative release rate of only TEfrom a channeled member. During testing, capsules containing 200 μl offormulation were placed in a 250 ml sink volume held at 37 degrees C.The sink condition was maintained with 3% added Labrosol, and the sinksolution was replaced at each sampling time to maintain sink conditions.A constant release with average rates of approximately 1.1 mg-2.4 mg perday observed in all samples.

FIGS. 13-21 are graphs of a cumulative release rate of testosteroneenanthate (TE) from a channeled member of with nanochannel heights of160 nm, 190 nm, 200 nm, 210 nm, 220 nm, and 250 nm, and with and withouta hydrophilic surface treatment included. During testing, capsulescontaining 200 μl of formulation were again placed in a 250 ml sinkvolume held at 37 degrees C. The sink condition was maintained with 3%added Labrosol, and the sink solution was replaced at each sampling timeto maintain sink conditions. It is a surprising result of thisdisclosure that immiscible formulations within the reservoir have adiffusion rate that has low sensitivity to both nanochannel height andto hydrophobic/hydrophilic surface. This novel result of combining achanneled member with a solubilizer significantly adds to the utilityand range of application of this disclosure.

FIG. 22 is a graph of serum concentration of testosterone in vivo. Threeformulations were used: TE, TE:Sesame Oil:Labrosol and TE:Vitamin ETPGS. As shown in the legend, the test subjects included intact rats(Intact), castrated rats treated with a solid testosterone pelletimplant (Pellet), castrated rats treated with a saline-filled implant(PBS), castrated rats treated with TE-only implants (TE), castrated ratswith TE:sesame oil:labrosol (8:1:1) (TESOLA), and castrated rats withTE:Vitamin E TPGS (9:1) (TEVE). The formulations according to thisdisclosure are observed to provide significant testosterone serum levelswhile avoiding the typical “burst effect” observed in other implants andinjections.

In particular embodiments, the therapeutic agent may comprise one ormore of the following substances: adrenergic agent; adrenocorticalsteroid; adrenocortical suppressant; aldosterone; alkylating agent;antagonist; amino acid; anabolic; analeptic; analgesic; analgesicagonists and antagonists; anesthetic; anorexogenic; anti-acne agent;anti-adrenergic; anti-allergic; anti-alopecia agent; anti-amebic;anti-anemic; anti-anginal; antiangiogenic, anti-anxiety; anti-arthritic;anti-asthmatic; anti-atherosclerotic; antibacterial; antibiotic;anticancer; anticholinergic; anticoagulant; anticonvulsant;antidepressant; antidiabetic; antidiarrheal; antidiuretic;anti-dyskinetic; anti-emetic; anti-epileptic; antifibrinolytic;antifungal; anti-hemorrhagic; antihistamine; anti-hypercalcemic,anti-hypercholesterolaemic; anti-hyperlipidaemic; anti-hypertensive;anti-hypertriglyceridemic; anti-hypotensive; anti-infective;anti-inflammatory; anti-ischemic; antimicrobial; antimigraine;antimitotic; antimycotic; anti-nauseant; anti-neoplastic;anti-neutropenic; anti-obesity agent; anti-osteoporotic, antiparasitic;antiproliferative; antipsychotic; antiretroviral; anti-resorptives;anti-rheumatic; anti-seborrheic; antisecretory; antispasmodic;antisclerotic; antithrombotic; antitumor; anti-ulcerative; antiviral;appetite suppressant; bisphosphonate; blood glucose regulator;bronchodilator; cardiovascular agent; central nervous system agent;contraceptive; cholinergic; concentration aid; depressant; diagnosticaid; diuretic; DNA-containing agent, dopaminergic agent; estrogenreceptor agonist; fertility agent; fibrinolytic; fluorescent agent; freeoxygen radical scavenger; gastric acid suppressant; gastrointestinalmotility effector; glucocorticoid; glutamatergic agent; hair growthstimulant; hemostatic; histamine H2 receptor antagonist; hormone; hypocholesterolemic; hypoglycemic; hypolipidemic; hypotensive; imagingagent; immunizing agent; immunomodulator; immunostimulant;immunosuppressant; interleukin, keratolytic; LHRH agonist; moodregulator; mucolytic; mydriatic; nasal decongestant; neuromuscularblocking agent; neuroprotective; NMDA antagonist; non-hormonal sterolderivative; nootropic agent; opioids; parasympathomimetic agent;plasminogen activator; platelet activating factor antagonist; plateletaggregation inhibitor; platinum-containing agent, psychotropic;radioactive agent; raf antagonist, RNA-containing agent, scabicide;sclerosing agent; sedative; sedative-hypnotic; selective adenosine A1antagonist; selective estrogen receptor modulator, serotonin antagonist;serotonin inhibitor; serotonin receptor antagonist; steroid; stimulant;thrombic agent; thyroid hormone; thyroid inhibitor; thyromimetic;tranquilizer; vasoconstrictor; vasodilator; wound healing agent;xanthine oxidase inhibitor; and the like; Abacavir, Abacavir sulfate,abatacept, Acarbose, Acetaminophen, Aciclovir, Adalimumab, Adapalene,Alendronate, Alendronate sodium, Alfuzosin, aliskiren, allopurinol,alvimopan, ambrisentan, Aminocaproic acid, Amitriptyline hydrochloride,amlodipine, amlodipine besylate, amoxicillin, amoxicilline, Amphetamine,Anastrozole, Aripiprazole, armodafinil, Atazanavir, atenolol,Atomoxetine, atorvastatin calcium, atorvastatin, Atropine sulfate,Azelastine, azithromycin, Balsalazide, Benazepril, bendamustinehydrochloride, Benzepril hydrochloride, bevacizumab, Bicalutamide,Bimatoprost, Bisoprolol, Bisoprolol fumarate, Bosentan, Botulin toxin,Budesonide, Buformin, Buprenorphine, Bupropion, bupropion hydrobromide,Bupropion Hydrochloride, Cabergoline, Calcipotriol, calcitriol,candesartan cilexetil, Capecitabine, Captopril, carbidopa, carisoprodol,Carvedilol, Caspofungin, Cefdinir, Cefoperazone, Cefotiam, cefprozil,Cefuroxime, Celecoxib, cephalaxin, Certolizumab Pegol, Cetirizine,Cetrizine hydrochloride, Cetuximab, Chlorpromazine hydrochloride,Chlorpheniramine maleate, ciclesonide, Cilastatin, cimetidine,Cinacalcet, Ciprofloxacin, citalopram hydrobromide, Clarithromycin,Clindamycin, Clindamycin, clindamycin hydrochloride, Clomipraminehydrochloride, Clonidine hydrochloride, clopidogrel, Clopidogrelbisulfate, Cloxacillin Sodium, Co-Amoxiclav, Codeine phosphate,Colchicines, Colesevelam, cyclobenzaprine hydrochloride,Cyclophosphamide, Cyclosporine, darbepoetin alfa, Darifenacin, DCRM 197protein, Desloratadine, desloratidine, Desmopressin sulfate,Desoximetasone, dexamethasone, Diclofenac, Diethylcarbamazine citrate,difluprednate, diphenhydramine, Dipyridamole, DL-methionine, Docetaxel,Donepezil, doripenem, Dorzolamide, Doxazosin, doxazosin mesylate,doxycydine, Drospirenone, Duloxetine, Dutasteride, eculizumab,Efavirenz, Emtricitabine, Enalapril, enalapril maleate, EnoxaparinSodium, Eprosartan, Erlotinib, Erythromycin, Erythropoetin,Escitalopram, esomeprazole, estradiol, Estrogen, Eszopiclone,etanercept, Ethembutol hydrochloride, Ethosuximide, ethynl estradiol,etonogestrel, etoricoxib, etravirine, Exenatide, Ezetimibe, Ezetimibe,Factor VII, famotidine, Famotidine, Fenofibrate, Fenofibrate, Fentanyl,Fentanyl citrate, Ferrous sulfate, Fexofenadine, fexofenadinehydrochloride, Filgrastim, Finasteride, fluconazole, Fluoxetinehydrochloride, Fluticasone, Fluvastatin, folic acid, Follitropin alfa,Follitropin beta, Formoterol, Fosinopril sodium, Gabapentin, Gabapentin,Gemcitabine, glargine insulin, Glatiramer, glimepride, Goserelin,histrelin acetate, Human growth hormone, Hydralazine hydrochloride,Hydrocodone bitartrate, Hydroxyurea, Hydroxyzine hydrochloride,Ibandronate, Imatinib, Imiglucerase, Imipenem, imiquimod, Indinavirsulfate, infliximab, Interferon beta-1a, Ipratropium, Irbesartan,Irinotecan, Isoniazid, Isosorbide moninitrate, ixabepilone, ketamine,ketoconazole, Ketorolac, Lactobionate, Lamivudine, Lamivudine,Lamotrigine, lanreotide acetate, Lansoprazole, lapatinib, laropiprant,Latanoprost, Letrozole, Leuprolide, Levalbuterol, Levamisolehydrochloride, Levetiracetam, levocetirizine dihydrochloride, levodopa,Levofloxacin, levonorgestrel, Levothyroxine, levothyroxine sodium,Lidocaine, Linezolid, Lisdexamfetamine Dimesylate, Lisinopril, Lisproinsulin, Lopinavir, Loratadine, lorazepam, Losartan potassium,maraviroc, Marinol, meclizine hydrochloride, Meloxicam, Memantine,Meropenem, metaxalone, metformin, Metformin Hydrochloride, methadone,methoxy polyethylene glycol-epoetin beta, Methylphenidate,Methylphenidate hydrochloride, Metoprolol, Metoprolol tartrate,metronidazole, Metronidazole, miglitol, Minocycline, Minocyclinehydrochloride, mirtazepine, Modafinil, Mometasone, montelukast,Montelukast sodium, Morphine, Moxifloxacin, Mycophenolate mofetil,Naloxone, Naproxen sodium, natalizumab, Neostigmine bromide, Niacin,Nicotinamide, Nifedipine, Nifurtimox, nilotinib hydrochloridemonohydrate, nitrofurantoin, Nortriptyline hydrochloride, nystatin,olanzapine, Olanzepine, Olmesartan, olmesartan medoxomil, olopatadinehydrochloride, Omalizumab, Omega-3 acid ethyl esters, Omeprazole,Ondansetron, Opioids, Opoid Antagonists, Orlistat, Oseltamivir,Oxaliplatin, Oxcarbazepine, Oxybytynin chloride, oxycodonehydrochloride, Paclitaxel, Palivizumab, Pantoprazole, paracetamol,Paroxetine, paroxetine hydrochloride, Pegylated interferon alfa-2a,Pemetrexed, Penicillamine, Penicillin V potassium, Phenformin, Phenyloinsodium, Pioglitazone, Piperacillin, Potassium chloride, Pramipexole,Pravastatin, Pravastatin sodium, prednisolone quetiapine fumerate,Pregabalin, Primaquine phosphate, Progesterone, Promethazine,Promethazine hydrochloride, Proponolol hydrochloride, Propoxyphenehydrochloride, pseudoephedrine, Pseudophedrine hydrochloride,Pyridostigmine bromide, Pyridoxine hydrochloride, Quetiapine, quetiapinefumarate, Quinapril hydrochloride, Rabeprazole, raloxifene, raltegravir,Ramipril, Ranitidine, Ranitidine hydrochloride, Recombinant factor VIII,retapamulin, Rimonabant, Risedronate, Risedronate sodium, risperidone,Ritonavir, rituximab, Rivastigmine, rivastigmine tartrate, Rizatriptan,Ropinirole, rosiglitazone, Rosiglitazone maleate, Rosuvastatin,Rotavirus vaccine, rotigotine, Salbutamol, Salbutamol sulfate,salmeterol, sapropterin dihydrochloride, Sertraline, sertralinehydrochloride, Sevelamer, Sevoflurane, Sildenafil, sildenafil citrate,simvastatin, Simvastatin, Sitagliptin, Sodium valproate, Solifenacin,Somatostatin, Somatropin, Stavudine, Sulfomethoxazole, Sumatriptan,Sumatriptan succinate, Tacrolimus, Tadalafil, tamoxifen citrate,Tamsulosin, tamsulosin hydrochloride, Tegaserod, Telmisartan, temazepam,Temozolomide, temsirolimus, Tenofovir, Terazosin Hydrochloride,Terbinafine, Teriparatide, testosterone, Tetracycline hydrochloride,Thalidomide, thymopentin, Timolol meleate, Tiotropium, tipranavir,Tolterodine, tolterodine tartrate, topiramate, topotecan, Tramadol,Tramodol hydrochloride, trastuzumab, trazodone hydrochloride,trimethoprim, Valaciclovir, Valacyclovir hydrochloride, Valproatesemisodium, valsartan, Vancomycin, Vardenafil, Varenicline, venlafaxine,Venlafaxine hydrochloride, Verapamil Hydrochloride, vildagliptin,Voglibose, Voriconazole, Wafarin sodium acetylsalicylic acid, Zaleplon,Zidovudine, Ziprasidone, Zoledronate, Zolpidem, or pharmaceuticallyacceptable salts thereof; 16-alpha fluoroestradiol, 17-alphadihydroequilenin, 17-alpha estradiol, 17-beta estradiol,17-hydroxyprogesterone, 1-dodecpyrrolidinone, 22-oxacalcitriol,3-isobutyl-gammabutyric acid, 6-fluoroursodeoxycholic acid,7-methoxytacrine, Abacavir, Abacavir sulfate, Abamectin, abanoquil,abatacept, abecarnil, abiraterone, Ablukast, Ablukast Sodium, Acadesine,acamprosate, Acarbose, Acebutolol, Acecamide Hydrochloride, Aceclidine,aceclofenae, Acedapsone, Acedapsone, Aceglutamide Aluminum, Acemannan,Acetaminophen, Acetazolamide, Acetohexamide, Acetohydroxamic Acid,acetomepregenol, Acetophenazine Maleate, Acetosulfone Sodium,Acetylcholine Chloride, Acetylcysteine, acetyl-L-carnitine,acetylmethadol, Aciclovir, Acifran, acipimox, acitemate, Acitretin,Acivicin, Aclarubicin, aclatonium, Acodazole Hydrochloride, aconiazide,Acrisorcin, Acrivastine, Acronine, Actisomide, Actodigin, Acyclovir,acylfulvene, Adatanserin Hydrochloride, adafenoxate, Adalimumab,Adapalene, adatanserin, adecypenol, adecypenol, Adefovir, adelmidrol,ademetionine, Adenosine, Adinazolam, Adipheinine Hydrochloride,adiposin, Adozelesin, adrafinil, Adrenalone, Aiclometasone Dipropionate,airbutamine, alacepril, Alamecin, Alanine, Alaproclate, alaptide,Albendazole, albolabrin, Albuterol, Alclofenae, Alcloxa, aldecalmycin,Aldesleukin, Aldioxa, Aletamine Hydrochloride, Alendronate, AlendronateSodium, alendronic acid, alentemol, Alentemol Hydrobromide, AleuroniumChloride, Alexidine, alfacalcidol, Alfentanil Hydrochloride, alfuzosin,Algestone Acetonide, alglucerase, Aliflurane, alinastine, Alipamide,aliskiren, Allantoin, Allobarbital, Allopurinol, Alonimid, alosetron,Alosetron Hydrochloride, Alovudine, Alpertine, alpha-idosone, Alpidem,Alprazolam, Alprenolol Hydrochloride, Alprenoxime Hydrochloride,Alprostadil, Alrestatin Sodium, Altanserin Tartrate, Alteplase,Althiazide, Altretamine, altromycin B, Alverinc Citrate, alvimopan,Alvircept Sudotox, Amadinone Acetate, Amantadine Hydrochloride,ambamustine, Ambomycin, ambrisentan, Ambruticin, Ambuphylline, Ambuside,Amcinafal, Amcinonide, Amdinocillin, Amdinocillin Pivoxil, AmedalinHydrochloride, amelometasone, Ameltolide, Amesergide, AmetantroneAcetate, amezinium metilsulfate, amfebutamone, Amfenac Sodium,Amfiutizole, Amicycline, Amidephrine Mesylate, amidox, Amifloxacin,amifostine, Amilcacin, Amiloride Hydrochloride, AminacrineHydrochloride, Aminobenzoate Potassium, Aminobenzoate Sodium,Aminocaproic Acid, Aminoglutethimide, Aminohippurate Sodium,aminolevulinic acid, Aminophylline, A minorex, Aminosalicylate sodium,Aminosalicylic acid, Amiodarone, Amiprilose Hydrochloride, AmiquinsinHydrochloride, amisulpride, Amitraz, Amitriptyline Hydrochloride,Amlexanox, amlodipine, amlodipine besylate, Amobarbital Sodium,Amodiaquine, Amodiaquine Hydrochloride, Amorolfine, Amoxapine,Amoxicillin, Amphecloral, Amphetamine, Amphetamine Sulfate, Amphomycin,Amphoterin B, Ampicillin, ampiroxieam, Ampyzine Sulfate, Amquinate,Amrinone, amrubicin, Amsacrine, Amylase, amylin, amythiamicin,Anagestone Acetate, anagrelide, Anakinra, ananain, anaritide, AnaritideAcetate, Anastrozole, Anazolene Sodium, Ancrod, andrographolide,Androstenedione, Angiotensin Amide, Anidoxime, Anileridine, AnilopamHydrochloride, Aniracetam, Anirolac, Anisotropine Methylbromide,Anistreplase, Anitrazafen, anordrin, antagonist D, antagonist G,antarelix, Antazoline Phosphate, Anthelmycin, Anthralin,Anthramyciantiandrogen, antiestrogen, antineoplaston, Antipyrine,antisense oligonucleotides, apadoline, apafant, Apalcillin Sodium,apaxifylline, Apazone, aphidicolin glycinate, Apixifylline, ApomorphineHydrochloride, apraclonidine, Apraclonidine Hydrochloride, Apramycin,Aprindine, Aprindine Hydrochloride, aprosulate sodium, Aprotinin,Aptazapine Maleate, aptiganel, apurinic acid, apurinic acid,aranidipine, Aranotin, Arbaprostil, arbekicin, arbidol, ArbutamineHydrochloride, Arclofenin, Ardeparin Sodium, argatroban, Arginine,Argipressin Tannate, Arildone, Aripiprazole, armodafinil, arotinolol,Arpinocid, Arteflene, Artilide Fumarate, asimadoline, aspalatone,Asparaginase, Aspartic Acid, Aspartocin, asperfuran, Aspirin,aspoxicillin, Asprelin, Astemizole, Astromicin Sulfate, asulacrine,atamestane, Atazanavir, Atenolol, atevirdine, Atipamezole, AtiprosinMaleate, Atolide, Atomoxetine, atorvastatin, Atorvastatin Calcium,Atosiban, Atovaquone, atpenin B, Atracurium Besylate, atrimustine,atrinositol, Atropine, Atropine sulfate, Auranofin, aureobasidin A,Aurothioglucose, Avilamycin, Avoparcin, Avridine, Axid, axinastatin 1,axinastatin 2, axinastatin 3, Azabon, Azacitidinie, AzaclorzineHydrochloride, Azaconazole, azadirachtine, Azalanstat Dihydrochloride,Azaloxan Fumarate, Azanator Maleate, Azanidazole, Azaperone, Azaribine,Azaserine, azasetron, Azatadine Maleate, Azathioprine, AzathioprineSodium, azatoxin, azatyrosine, azelaic acid, Azelastine, azelnidipine,Azepindole, Azetepa, azimilide, Azithromycin, Azlocillin, Azolimine,Azosemide, Azotomycin, Aztreonam, Azumolene Sodium, BacampicillinHydrochloride, baccatin III, Bacitracin, Baclofen, bacoside A, bacosideB, bactobolamine, balanol, balazipone, balhimycin, balofloxacin,balsalazide, Bambermycins, bambuterol, Bamethan Sulfate, BamifyllineHydrochloride, Bamidazole, baohuoside 1, Barmastine, barnidipine, Basic,Basifungin, Batanopride Hydrochloride, batebulast, Batelapine Maleate,Batimastat, beau vericin, Becanthone Hydrochloride, becaplermin,becliconazole, Beclomethasone Dipropionate, befloxatone, Beinserazide,Belfosdil, Belladonna, Beloxamide, Bemesetron, Bemitradine, Bemoradan,Benapryzine Hydrochloride, Benazepril, Benazepril Hydrochloride,Benazeprilat, Benda calol Mesylate, bendamustine hydrochloride,Bendazac, Bendroflumethiazide, benflumetol, benidipine, Benorterone,Benoxaprofen, Benoxaprofen, Benoxinate Hydrochloride, Benperidol,Bentazepam, Bentiromide, Benurestat, Benzbromarone, Benzeprilhydrochloride, Benzethonium Chloride, Benzetimide Hydrochloride,Benzilonium Bromide, Benzindopyrine Hydrochloride, benzisoxazole,Benzocaine, benzochlorins, Benzoctamine Hydrochloride, Benzodepa,benzoidazoxan, Benzonatate, Benzoyl Peroxide, benzoylstaurosporine,Benzquinamide, Benzthiazide, benztropine, Benztropine Mesylate,Benzydamine Hydrochloride, Benzylpenicilloyl Polylysine, bepridil,Bepridil Hydrochloride, Beractant, Beraprost, Berefrine, berlafenone,bertosamil, Berythromycin, besipirdine, betaalethine, betaclamycin B,Betamethasone, betamipron, betaxolol, Betaxolol Hydrochloride,Bethanechol Chloride, Bethanidine Sulfate, betulinic acid, bevacizumab,bevantolol, Bevantolol Hydrochloride, Bezafibrate, BialamicolHydrochloride, Biapenem, Bicalutamide, Bicifadine Hydrochloride,Biclodil Hydrochloride, Bidisomide, bifemelane, Bifonazole, bimakalim,Bimatoprost, bimithil, Bindarit, Biniramycin, binospirone, bioxalomycin,Bipenamol Hydrochloride, Biperiden, Biphenamine Hydrochloride,biriperone, bisantrene, bisaramil, bisaziridinylspermine,bis-benzimidzole A, bis-benzimidazole B, bisnafide, Bisobrin Lactate,Bisoprolol, Bisoprolol fumarate, Bispyrithione Magsulfex, bistramide D,bistramide K, bistratene A, Bithionolate Sodium, Bitolterol Mesylate,Bivalirudin, Bizelesin, Bleomycin Sulfate, boldine, BolandiolDipropionate, Bolasterone, Boldenone Undecylenate, Bolenol,Bolmantalate, bopindolol, Bosentan, Botulin toxin, Boxidine, brefeldin,breflate, Brequinar Sodium, Bretazenil, Bretylium Tosylate, BrifentanilHydrochloride, brimonidine, Brinolase, Brocresine, Brocrinat, Brofoxine,Bromadoline Maleate, Bromazepam, Bromchlorenone, Bromelain, bromfenac,Brominidione, Bromocriptine, Bromodiphenhydramine Hydrochloride,Bromoxanide, Bromperidol, Bromperidol Decanoate, BrompheniramineMaleate, Broperamole, Bropirimine, Brotizolam, Bucamide Maleate,bucindolol, Buclizine Hydrochloride, Bucromar one, Budesonide, budipine,budotitane, Buformin, Bumetanide, Bunaprolast, bunazosin, BunololHydrochloride, Bupicomide, Bupivacaine Hydrochloride, Buprenorphine,Buprenorphine Hydrochloride, Bupropion, bupropion hydrobromide,Bupropion Hydrochloride, Buramate, Buserelin Acetate, BuspironeHydrochloride, Busulfan, Butabarbital, Butacetin, ButaclamolHydrochloride, Butalbital, Butamben, Butamirate Citrate, Butaperazine,Butaprost, Butedronate Tetrasodium, butenafine, Buterizine, buthionincsulfoximine, Butikacin, Butilfenin, Butirosin Sulfate, Butixirate,butixocort propionate, Butoconazole Nitrate, Butonate, Butopamine,Butoprozine Hydrochloride, Butorphanol, Butoxamine Hydrochloride,Butriptyline Hydrochloride, Cabergoline, Cactinomycin, Cadexomer Iodine,Caffeine, calanolide A, Calcifediol, Calcipotriene, calcipotriol,Calcitonin, Calcitriol, Calcium Undecylenate, calphostin C, Calusterone,Cambendazole, Cammonam Sodium, camonagrel, canary pox IL-2, candesartan,candesartan cilexetil, Candicidin, candoxatril, candoxatrilat,Caniglibose, Canrenoate Potassium, Canrenone, capecitabine, CapobenateSodium, Capobenic Acid, Capreomycin Sulfate, capromab, capsaicin,Captopril, Capuride, Car bocysteine, Caracemide, Carbachol, Carbadox,Carbamazepine, Carbamide Peroxide, Carbantel Lauryl Sulfate, CarbaspirinCalcium, Carbazeran, carbazomycin C, Carbenicillin Potassium,Carbenoxolone Sodium, Carbetimer, carbetocin, Carbidopa,Carbidopa-Levodopa, Carbinoxamine Maleate, Carbiphene Hydrochloride,Carbocloral, Carbol-Fuchsin, Carboplatin, Carboprost, carbovir,carboxamide-amino-triazo-1e, carboxyamidotriazole, carboxymethylatedbeta-1,3-glucan, Carbuterol Hydrochloride, CaRest M3, CarfentanilCitrate, Carisoprodol, Carmantadine, Carmustine, CARN 700, Carnidazole,Caroxazone, carperitide, Carphenazine Maleate, Carprofen, CarsatrinSuccinate, Cartazolate, carteolol, Carteolol Hydrochloride, CarubicinHydrochloride, carvedilol, carvotroline, Carvotroline Hydrochloride,carzelesin, Caspofungin, castanospermine, caurumonam, cebaracetam,cecropin B, Cedefingol, Cefaclor, Cefadroxil, Cefamandole, Cefaparole,Cefatrizine, Cefazaflur Sodium, Cefazolin, cefcapene pivoxil,cefdaloxime pentexil tosilate, Cefdinir, cefditoren pivoxil, Cefepime,cefetamet, Cefetecol, cefixime, cefluprenam, Cefinenoxime Hydrochloride,Cefinetazole, cefminlox, cefodizime, Cefonicid Sodium, Cefoperazone,Cefoperazone Sodium, Ceforanide, cefoselis, Cefotaxime Sodium,Cefotetan, cefotiam, Cefoxitin, cefozopran, cefpimizole, Cefpiramide,cefpirome, cefpodoxime proxetil, cefprozil, Cefroxadine, cefsulodin,Ceftazidime, cefteram, ceftibuten, Ceftizoxime Sodium, ceftriaxooe,Cefuroxime, celastrol, Celecoxib, celikalim, celiprolol, cepacidiine A,Cephacetrile Sodium, Cephalexin, Cephaloglycin, Cephaloridine,Cephalothin Sodium, Cephapirin Sodium, Cephradine, cericlamine,cerivastatin, Ceruletide, Ceronapril, Certolizumab Pegol, certoparinsodium, Cetaben Sodium, Cetalkonium Chloride, Cetamolol Hydrochloride,Cethuperazone, cetiedil, cetirizine, Cetophenicol, CetraxateHydrochloride, Cetrizine hydrochloride, cetrorelix, Cetuximab,Cetylpyridinium Chloride, Chenodiol, Chlophedianol Hydrochloride,Chloral Betaine, Chlorambucil, Chloramphenicol, Chlordantoin,Chlordiazepoxide, Chlorhexidine Gluconate, chlorins, ChlormadinoneAcetate, chloroorienticin A, Chloroprocaine Hydrochloride,Chloropropamide, Chloroquine, chloroquinoxaline sulfonamide,Chlorothiazide, Chlorotrianisene, Chloroxine, Chloroxylenol,Chlorpheniramine Maleate, Chlorphenesin Carbamate, Chlorpheniraminemaleate, Chlorpromazine, Chlorpromazine hydrochloride, Chlorpropamide,Chlorprothixene, Chlortetracycline Bisulfate, Chlorthalidone,Chlorzoxazone, Cholestyramine Resin, Chromonar Hydrochloride,cibenzoline, cicaprost, Ciclafrine Hydrochloride, Ciclazindol,ciclesonide, cicletanine, Ciclopirox, Cicloprofen, cicloprolol,Cidofovir, Cidoxepin Hydrochloride, Cifenline, Ciglitazone, CiladopaHydrochloride, cilansetron, Cilastatin, Cilastatin Sodium, Cilazapril,cilnidipine, Cilobamine Mesylate, cilobradine, Cilofungin, cilostazol,Cimaterol, Cimetidine, cimetropium bromide, Cinacalcet, Cinalukast,Cinanserin Hydrochloride, Cinepazet Maleate, Cinflumide, Cingestol,cinitapride, Cinnamedrine, Cinnarizine, cinolazepam, Cinoxacin,Cinperene, Cinromide, Cintazone, Cintriamide, Cioteronel, Cipamfylline,Ciprefadol Succinate, Ciprocinonide, Ciprofibrate, Ciprofloxacin,ciprostene, Ciramadol, Cirolemycin, Cisplatin, cisapride, cisatracuriumbesilate, Cisconazole, cis-porphyrin, cistinexine, citalopram,citalopram hydrobromide, Citenamide, citicoline, citreamicin alpha,cladribine, Clamoxyquin Hydrochloride, Clarithromycin, clausenamide,Clavulanate Potassium, Clazolam, Clazolimine, clebopride, Clemastine,Clentiazem Maleate, Clidinium Bromide, clinafloxacin, Clindamycin,clindamycin hydrochloride, Clioquinol, Clioxanide, Cliprofen, clobazam,Clobetasol Propionate, Clobetasone Butyrate, Clocortolone Acetate,Clodanolene, Clodazon Hydrochloride, clodronic acid, Clofazimine,Clofibrate, Clofilium Phosphate, Cloge stone Acetate, ClomacranPhosphate, Clomegestone Acetate, Clometherone, clomethiazole,clomifeneanalogues, Clominorex, Clomiphene, Clomipramine Hydrochloride,Clonazepam, Clonidine, Clonidine hydrochloride, Clonitrate, Clonixeril,Clonixin, Clopamide, Clopenthixol, Cloperidone Hydrochloride,clopidogrel, Clopidogrel bisulfate, Clopimozide, Clopipazan Mesylate,Clopirac, Cloprednol, Cloprostenol Sodium, Clorazepate Dipotassium,Clorethate, Clorexolone, Cloroperone Hydrochloride, ClorprenalineHydrochloride, Clorsulon, Clortemine Hydrochloride, Closantel,Closiramine Aceturate, Clothiapine, Clothixamide Maleate CloticasonePropionate, Clotrimazole, Cloxacillin Benzathine, Cloxacillin Sodium,Cloxyquin, Clozapine, Co-Amoxiclav, Cocaine, Coccidioidin, Codeine,Codeine phosphate, Codoxime, Colchicine, Colesevelam, colestimide,Colestipol Hydrochloride, Colestolone, Colforsin, Colfosceril Palmitate,Colistimethate Sodium, Colistin Sulfate, collismycin A, collismycin B,Colterol Mesylate, combretastatin A4, complestatin, conagenin,Conorphone Hydrochloride, contignasterol, contortrostatin, CormethasoneAcetate, Corticorelin Ovine Tnflutate, Corticotropin, Cortisone Acetate,Cortivazol, Cortodoxone, cosalane, costatolide, Cosyntropin, cotinine,Coumadin, Coumermycin, crambescidin, Crilvastatin, crisnatol, CromitrileSodium, Cromolyn Sodium, Crotamiton, cryptophycin, cucumariosid,Cuprimyxin, curacin A, curdlan sulfate, curiosin, Cyclacillin,Cyclazocine, cyclazosin, Cyclindole, Cycliramine Maleate, Cyclizine,Cyclobendazole, cyclobenzaprine, cyclobenzaprine hydrochloride, cyclobutA, cyclobut G, cyclocapron, Cycloguanil Pamoate, Cycloheximide,cyclopentanthraquinones, Cyclopenthiazide, Cyclopentolate Hydrochloride,Cyclophenazine Hydrochloride, Cyclophosphamide, cycloplatam,Cyclopropane, Cycloserine, cyclosin, Cyclosporine, cyclothialidine,Cyclothiazide, cyclothiazomycin, Cyheptamide, cypemycin, CyponamineHydrochloride, Cyprazepam, Cyproheptadine Hydrochloride, CyprolidolHydrochloride, cyproterone, Cyproximide, Cysteamine, CysteineHydrochloride, Cystine, Cytarabine, Cytarabine Hydrochloride, cytarabineocfosfate, cytochalasin B, cytostatin, Dacarbazine, dacliximab,dactimicin, Dactinomycin, daidzein, Daledalin Tosylate, dalfopristin,Dalteparin Sodium, Daltroban, Dalvastatin, danaparoid, Danazol,Dantrolene, daphlnodorin A, dapiprazole, dapitant, DapoxetineHydrochloride, Dapsone, Daptomycin, darbepoetin alfa, DarglitazoneSodium, darifenacin, darlucin A, Darodipine, darsidomine, DaunorubicinHydrochloride, Dazadrol Maleate, Dazepinil Hydrochloride, Dazmegrel,Dazopride Fumarate, Dazoxiben Hydrochloride, DCRM 197 protein,Debrisoquin Sulfate, Decitabine, deferiprone, deflazacort, DehydrocholicAcid, dehydrodidemnin B, Dehydroepiandrosterone, delapril, DelaprilHydrochloride, Delavirdine Mesylate, delequamine, delfaprazine,Delmadinone Acetate, delmopinol, delphinidin, Demecarium Bromide,Demeclocycline, Demecycline, Demoxepam, Denofungin, deoxypyridinoline,Depakote, deprodone, Deprostil, depsidomycin, deramciclane, dermatansulfate, Desciclovir, Descinolone Acetonide, Desfurane, DesipramineHydrochloride, desirudin, Deslanoside, Desloratadine, deslorelin,desmopressin, Desmopressin sulfate, desogestrel, Desonide,Desoximetasone, desoxoamiodarone, Desoxy-corticosterone Acetate,detajmium bitartrate, Deterenol Hydrochloride, Detirelix Acetate,Devazepide, Dexamethasone, Dexamisole, Dexbrompheniramine Maleate,Dexchlorpheniramine Maleate, Dexclamol Hydrochloride, Dexetimide,Dexfenfluramine Hydrochloride, dexifosfamide, Deximafen, dexketoprofen,dexloxiglumide, Dexmedetomidine, Dexormaplatin, DexoxadrolHydrochloride, Dexpanthenol, Dexpemedolac, Dexpropranolol Hydrochloride,Dexrazoxane, dexsotalol, dextrin 2-sulphate, Dextroamphetamine,Dextromethorphan, Dextrorphan Hydrochloride, Dextrothyroxine Sodium,dexverapamil, Dezaguanine, dezinamide, dezocine, DiacetololHydrochloride, Diamocaine Cyclamate, Diapamide, Diatrizoate Meglumine,Diatrizoic Acid, Diaveridine, Diazepam, Diaziquone, Diazoxide,Dibenzepin Hydrochloride, Dibenzothiophene, Dibucaine, Dichliorvos,Dichloralphenazone, Dichlorphenamide, Dicirenone, Diclofenac, DiclofenacSodium, Dicloxacillin, dicranin, Dicumarol, Dicyclomine Hydrochloride,Didanosine, didemnin B, didox, Dienestrol, dienogest, DiethylcarbamazineCitrate, diethylhomospermine, diethylnorspermine, DiethylpropionHydrochloride, Diethylstilbestrol, Difenoximide Hydrochloride,Difenoxin, Diflorasone Diacetate, Difloxacin Hydrochloride, DifluanineHydrochloride, Diflucortolone, Diflumidone Sodium, Diflunisal,Difluprednate, Diftalone, Digitalis, Digitoxin, Digoxin, DihexyverineHydrochloride, dihydrexidine, dihydro-5-azacytidine, DihydrocodeineBitartrate, Dihydroergotamine Mesylate, Dihydroestosterone,Dihydrostreptomycin Sulfate, Dihydrotachysterol, Dilantin, DilevalolHydrochloride, Diltiazem Hydrochloride, Dimefadane, DimeflineHydrochloride, Dimenhydrinate, Dimercaprol, Dimethadione, DimethindeneMaleate, Dimethisterone, Dimethyl Sulfoxide, dimethylhomospermine,dimethylprostaglandin A1, dimiracetam, Dimoxamine Hydrochloride,Dinoprost, Dinoprostone, Dioxadrol Hydrochloride, dioxamycin,diphenhydramine, Diphenhydramine Citrate, Diphenidol, DiphenoxylateHydrochloride, diphenylspiromustine, Dipivefin Hydrochloride,Dipivefrin, dipliencyprone, diprafenone, dipropylnorspermine,Dipyridamole, Dipyrithione, Dipyrone, dirithromycin, discodermolide,Disobutamide, Disofenin, Disopyramide, Disoxaril, disulfuram, Ditekiren,Divalproex Sodium, Dizocilpine Maleate, DL-methionine, Dobutamine,docarpamine, Docebenone, Docetaxel, Doconazole, docosanol, dofetilide,dolasetron, Donepezil, doripenem, Dorzolamide, Doxazosin, doxazosinmesylate, doxycydine, Drospirenone, Duloxetine, Dutasteride, Ebastine,ebiratide, ebrotidine, ebselen, ecabapide, ecabet, ecadotril,ecdisteron, echicetin, echistatin, Echothiophate Iodide, EclanamineMaleate, Eclazolast, ecomustine, Econazole, ecteinascidin 722,eculizumab, edaravone, Edatrexate, edelfosine, Edifolone Acetate,edobacomab, Edoxudine, edrecolomab, Edrophonium Chloride,edroxyprogesteone Acetate, Efavirenz, efegatran, eflornithine,efonidipine, egualcen, Elantrine, eleatonin, elemene, eletriptan,elgodipine, eliprodil, Elsamitrucin, eltenae, Elucaine, emailcalim,emedastine, Emetine Hydrochloride, emiglitate, Emilium Tosylate,emitefur, emoctakin, Emtricitabine, Enadoline Hydrochloride, Enailciren,enalapril, enalapril maleate, enazadrem, Encyprate, EndralazineMesylate, Endrysone, Enflurane, englitazone, Enilconazole, Enisoprost,Enlimomab, Enloplatin, Enofelast, Enolicam Sodium, Enoxacin, enoxacin,enoxaparin sodium, Enoxaparin Sodium, Enoximone, Enpiroline Phosphate,Enprofylline, Enpromate, entacapone, enterostatin, Enviradene,Enviroxime, Ephedrine, Epicillin, Epimestrol, Epinephrine, EpinephrylBorate, Epipropidine, Epirizole, epirubicin, EpitetracyclineHydrochloride, Epithiazide, Epoetin Alfa, Epoetin Beta, Epoprostenol,Epoprostenol Sodium, epoxymexrenone, epristeride, Eprosartan,eptastigmine, equilenin, Equilin, Erbulozole, erdosteine, ErgoloidMesylates, Ergonovine Maleate, Ergotamine Tartrate, Erlotinib,ersentilide, Ersofermin, erythritol, Erythrityl Tetranitrate,Erythromycin, Erythropoetin, Escitalopram, Esmolol Hydrochloride,esomeprazole, Esorubicin Hydrochloride, Esproquin Hydrochloride,Estazolam, Estradiol, Estramustine, Estrazinol Hydrobromide, Estriol,Estrofurate, Estrogen, Estrone, Estropipate, esuprone, Eszopiclone,Etafedrine Hydrochloride, etanercept, Etanidazole, etanterol, Etarotene,Etazolate Hydrochloride, Eterobarb, ethacizin, Ethacrynate Sodium,Ethacrynic Acid, Ethambutol Hydrochloride, Ethamivan, EthanolamineOleate, Ethehlorvynol, Ethembutol hydrochloride, Ethinyl estradiol,Ethiodized Oil, Ethionamide, Ethonam Nitrate, EthopropazineHydrochloride, Ethosuximide, Ethosuximide, Ethotoin, EthoxazeneHydrochloride, Ethybenztropine, Ethyl Chloride, Ethyl Dibunate,Ethylestrenol, Ethyndiol, Ethynerone, ethynl estradiol, EthynodiolDiacetate, Etibendazole, Etidocaine, Etidronate Disodium, EtidronicAcid, Etifenin, Etintidine Hydrochloride, etizolam, Etodolac,Etofenamate, Etoformin Hydrochloride, Etomidate, Etonogestrel,Etoperidone Hydrochloride, Etoposide, Etoprine, etoricoxib, EtoxadrolHydrochloride, Etozolin, etrabamine, etravirine, Etretinate, EtryptamineAcetate, Eucatropine Hydrochloride, Eugenol, Euprocin Hydrochloride,eveminomicin, Exametazime, examorelin, Exaprolol Hydrochloride,exemestane, Exenatide, Ezetimibe, Ezetimibe, Factor VII, fadrozole,faeriefungin, Famciclovir, Famotidine, Fampridine, fantofarone,Fantridone Hydrochloride, faropenem, fasidotril, fasudil, fazarabine,fedotozine, Felbamate, felbamate, Felbinac, Felodipine, Felypressin,Fenalamide, Fenamole, Fenbendazole, Fenbufen, Fencibutirol, Fenclofenac,Fenclonine, Fenclorac, Fendosal, Fenestrel, Fenethylline Hydrochloride,Fenfluramine Hydrochloride, Fengabine, Fenimide, Fenisorex, FenmetozoleHydrochloride, Fenmetramide, Fenobam, Fenoctimine Sulfate, Fenofibrate,fenoldopam, Fenoprofen, Fenoterol, Fenpipalone, FenprinastHydrochloride, Fenprostalene, Fenquizone, fenretinide, fenspiride,fentanyl, Fentanyl Citrate, Fentiazac, Fenticlor, fenticonazole,Fenyripol Hydrochloride, fepradinol, ferpifosate sodium, ferristene,ferrixan, Ferrous Sulfate, Ferumoxides, ferumoxsil, FetoxylateHydrochloride, Fexofenadine, fexofenadine hydrochloride, FezolamineFumarate, Fiacitabine, Fialuridine, fibmoxef, Fibrinogen, Filgrastim,Filipin, Finasteride, fiorfenicol, fiorifenine, fiosatidil, fiumecinol,fiunarizine, fiuparoxan, fiupirtine, fiurithromycin, fiutrimazole,fiuvastatin, fiuvoxamine, Flavodilol Maleate, flavopiridol, FlavoxateHydrochloride, Flazalone, flecamide, flerobuterol, Fleroxacin,flesinoxan, Flestolol Sulfate, Fletazepam, flezelastine, flobufen,Floctafenine, Flordipine, Flosequinan, Floxacillin, Floxuridine,fluasterone, Fluazacort, Flubanilate Hydrochloride, Flubendazole,Flucindole, Flucloronide, Fluconazole, Flucytosine, Fludalanine,Fludarabine Phosphate, Fludazonium Chloride, Fludeoxyglucose, Fludorex,Fludrocortisone Acetate, Flufenamic Acid, Flufenisal, Flumazenil,Flumequine, Flumeridone, Flumethasone, Flumetramide, Flumezapine,Fluminorex, Flumizole, Flumoxonide, Flunidazole, Flunisolide,Flunitrazepam, Flunixin, fluocalcitriol, Fluocinolone Acetonide,Fluocinonide, Fluocortin Butyl, Fluocortolone, Fluorescein,fluorodaunorunicin hydrochloride, Fluorodopa, Fluorometholone,Fluorouracil, Fluotracen Hydrochloride, Fluoxetine, Fluoxetinehydrochloride, Fluoxymesterone, Fluperamide, Fluperolone Acetate,Fluphenazine Decanoate, Fluprednisolone, Fluproquazone, FluprostenolSodium, Fluquazone, Fluradoline Hydrochloride, Flurandrenolide,Flurazepam Hydrochloride, Flurbiprofen, Fluretofen, Fluorocitabine,Fluorofamide, Fluorogestone Acetate, Fluorothyl, Fluoroxene,Fluspiperone, Fluspirilene, Fluticasone, Fluticasone Propionate,Flutroline, Fluvastatin, Fluvastatin Sodium, Fluzinamide, Folic Acid,Follicle regulatory protein, Folliculostatin, Follitropin alfa,Follitropin beta, Fomepizole, Fonazine Mesylate, forasartan, forfenimex,forfenirmex, formestane, Formocortal, formoterol, Fosarilate, Fosazepam,Foscarnet Sodium, fosfomycin, Fosfonet Sodium, fosinopril, Fosinoprilsodium, Fosinoprilat, fosphenyloin, Fosquidone, Fostedil, fostriecin,fotemustine, Fuchsin, Fumoxicillin, Fungimycin, Furaprofen,Furazolidone, Furazolium Chloride, Furegrelate Sodium, Furobufen,Furodazole, Furosemide, Fusidate Sodium, Fusidic Acid, Gabapentin,Gadobenate Dimeglumine, gadobenic acid, gadobutrol, Gadodiamide,gadolinium texaphyrin, Gadopentetate Dimegiumine, gadoteric acid,Gadoteridol, Gadoversetamide, galantamine, galdansetron, GaldansetronHydrochloride, Gallamine Triethiodide, gallium nitrate, gallopamil,galocitabine, Gamfexine, gamolenic acid, Ganciclovir, ganirelix,Gemcadiol, Gemcitabine, Gemeprost, Gemfibrozil, Gentamicin Sulfate,Gentian Violet, gepirone, Gestaclone, Gestodene, Gestonorone Caproate,Gestrinone, Gevotroline Hydrochloride, girisopam, glargine insulin,glaspimod, Glatiramer, glaucocalyxin A, Glemanserin, Gliamilide,Glibornuride, Glicetanile Sodium, Glifiumide, Glimepiride, Glipizide,Gloximonam, Glucagon, glutapyrone, Glutethimide, Glyburide, glycopine,glycopril, Glycopyrrolate, Glyhexamide, Glymidine Sodium, Glyoctamide,Glyparamide, Gold Au-198, Gonadoctrinins, Gonadorelin, Gonadotropins,Goserelin, Gramicidin, Granisetron, grepafloxacin, Griseofulvin,Guaiapate, Guaithylline, Guanabenz, Guanabenz Acetate, GuanadrelSulfate, Guancydine, Guanethidine Monosulfate, Guanfacine Hydrochloride,Guanisoquin Sulfate, Guanoclor Sulfate, Guanoctine Hydrochloride,Guanoxabenz, Guanoxan Sulfate, Guanoxyfen Sulfate, GusperimusTrihydrochloride, Halazepam, Halcinonide, halichondrin B, HalobetasolPropionate, halofantrine, Halofantrine Hydrochloride, Halofenate,Halofuginone Hydrobromide, halomon, Halopemide, Haloperidol,halopredone, Haloprogesterone, Haloprogin, Halothane, Halquinols,Hamycin, hatomamicin, hatomarubigin A, hatomarubigin B, hatomarubigin C,hatomarubigin D, Heparin Sodium, hepsulfam, heregulin, Hetacillin,Heterooium Bromide, Hexachlorophene Hydrogen Peroxide, HexafluoreniumBromide, hexamethylene bisacetamide, Hexedine, Hexobendine,Hexoprenaline Sulfate, Hexylresorcinol, Histamine Phosphate, Histidine,Histoplasmin, Histrelin, histrelin acetate, Homatropine Hydrobromide,Hoquizil Hydrochloride, Human chorionic gonadotropin, Human growthhormone, Hycanthone, Hydralazine Hydrochloride, Hydralazine Polistirex,Hydrochlorothiazide, Hydrocodone Bitartrate, Hydrocortisone,Hydroflumethiazide, Hydromorphone Hydrochloride, HydroxyamphetamineHydrobromide, Hydroxychloroquine Sulfate, Hydroxyphenamate,Hydroxyprogesterone Caproate, Hydroxyurea, Hydroxyzine Hydrochloride,Hymecromone, Hyoscyamine, hypericin, Ibafloxacin, Ibandronate, ibogaine,Ibopam, ibudilast, Ibufenac, Ibuprofen, Ibutilide Fumarate, IcatibantAcetate, Ichthammol, Icotidine, idarubicin, idoxifene, Idoxuridine,idramantone, Ifetroban, Ifosfamide, Ilepeimide, illimaquinone,ilmofosin, ilomastat, Ilonidap, iloperidone, iloprost, ImafenHydrochloride, Imatinib, Imazodan Hydrochloride, imidapril, imidazenil,imidazoacridone, Imidecyl Iodine, Imidocarb Hydrochloride, ImidolineHydrochloride, Imidurea, Imiglucerase, Imiloxan Hydrochloride, Imipenem,Imipramine Hydrochloride, imiquimod, Impromidine Hydrochloride,Indacrinone, Indapamide, Indecamide Hydrochloride, IndeloxazineHydrochloride, Indigotindisulfonate Sodium, indinavir, Indinavirsulfate, Indocyanine Green, Indolapril Hydrochloride, Indolidan,indometacin, Indomethacin Sodium, Indoprofen, indoramin, IndorenateHydrochloride, Indoxole, Indriline Hydrochloride, infliximab,inocoterone, inogatran, inolimomab, Inositol Niacinate, Insulin,Interferon beta-1a, Intrazole, Intriptyline Hydrochloride, iobenguane,Iobenzamic Acid, iobitridol, Iodine, iodoamiloride, iododoxorubicin,iofratol, iomeprol, iopentol, iopromide, iopyrol, iotriside, ioxilan,ipazilide, ipenoxazone, ipidacrine, Ipodate Calcium, ipomeanol,Ipratropium, Ipratropium Bromide, ipriflavone, Iprindole, Iprofenin,Ipronidazole, Iproplatin, Iproxamine Hydrochloride, ipsapirone,irbesartan, irinotecan, irloxacin, iroplact, irsogladin, Irtemazole,isalsteine, Isamoxole, isbogrel, Isepamicin, isobengazole, Isobutamben,Isocarboxazid, Isoconazole, Isoetharine, isofloxythepin, IsoflupredoneAcetate, Isoflurane, Isofluorophate, isohomohalicondrin B, Isoleucine,Isomazole Hydrochloride, Isomylamine Hydrochloride, Isoniazid,Isopropamide Iodide, Isopropyl Alcohol, isopropyl unoprostone,Isoproterenol Hydrochloride, Isosorbide, Isosorbide Mononitrate,Isotiquimide, Isotretinoin, Isoxepac, Isoxicam, IsoxsuprineHydrochloride, isradipine, itameline, itasetron, Itazigrel, itopride,Itraconazole, Ivermectin, ixabepilone, jasplakinolide, Jemefloxacin,Jesopitron, Josamycin, kahalalide F, Kalafungin, Kanamycin Sulfate,ketamine, Ketanserin, Ketazocine, Ketazolam, Kethoxal, KetipramineFumarate, Ketoconazole, Ketoprofen, Ketorfanol, ketorolac, KetotifenFumarate, Kitasamycin, Labetalol Hydrochloride, Lacidipine, lacidipine,lactitol, lactivicin, Lactobionate, laennec, lafutidine,1-alphahydroxyvitamin D2, lamellarin-N triacetate, lamifiban,Lamivudine, Lamotrigine, lanoconazole, Lanoxin, lanperisone, lanreotide,lanreotide acetate, Lansoprazole, lapatinib, laropiprant, latanoprost,lateritin, laurocapram, Lauryl Isoquinolinium Bromide, LavoltidineSuccinate, lazabemide, Lecimibide, leinamycin, lemildipine,leminoprazole, lenercept, Leniquinsin, lenograstim, Lenperone, lentinansulfate, leptin, leptolstatin, lercanidipine, Lergotrile, lerisetron,Letimide Hydrochloride, letrazuril, letrozole, Leucine, leucomyzin,leuprolide, Leuprolide Acetate, leuprorelin, Levalbuterol, LevamfetamineSuccinate, levamisole, Levdobutamine Lactobionate, Leveromakalim,levetiracetam, Leveycloserine, levobetaxolol, levobunolol,levobupivacaine, levocabastine, levocarnitine, levocetirizine,levocetirizine dihydrochloride, Levodopa, levodropropizine,levofloxacin, Levofuraltadone, Levoleucovorin Calcium, LevomethadylAcetate, Levomethadyl Acetate Hydrochloride, levomoprolol, LevonantradolHydrochloride, Levonordefrin, Levonorgestrel, LevopropoxypheneNapsylate, Levopropylcillin Potassium, levormeloxifene, LevorphanolTartrate, levosimendan, levosulpiride, Levothyroxine, LevothyroxineSodium, Levoxadrol Hydrochloride, Lexipafant, Lexithromycin, liarozole,Libenzapril, Lidamidine Hydrochloride, Lidocaine, Lidofenin,Lidoflazine, Lifarizin, Lifibrate, Lifibrol, Linarotene, Lincomycin,Linezolid, Linogliride, Linopirdine, linotroban, linsidomine,lintitript, lintopride, Liothyronine 1-125, liothyronine sodium,Liotrix, lirexapride, Lisdexamfetamine Dimesylate, lisinopril, Lisproinsulin, lissoclinamide, Lixazinone Sulfate, lobaplatin, LobenzaritSodium, Lobucavir, locarmate Meglumine, locarmic Acid, locetamic Acid,lodamide, Lodelaben, lodipamide Meglumine, lodixanol, IodoantipyrineI-131, Iodocholesterol I-131, Iodohippurate Sodium I-131, IodopyracetI-125, Iodoquinol, Iodoxamate Meglumine, lodoxamide, Iodoxamie Acid,Lofemizole Hydrochloride, Lofentanil Oxalate, Lofepramine Hydrochloride,lofetamine Hydrochloride I-123, Lofexidine Hydrochloride, loglicic Acid,loglucol, loglucomide, loglycamic Acid, logulamide, lohexyl, lombricine,Lomefloxacin, lomerizine, lomethin I-125, Lometraline Hydrochloride,lometrexol, Lomofungin, Lomoxicam, Lomustine, Lonapalene, lonazolac,lonidamine, lopamidol, lopanoic Acid, Loperamide Hydrochloride,lophendylate, Lopinavir, loprocemic Acid, lopronic Acid, lopydol,lopydone, loracarbef, Lorajmine Hydrochloride, loratadine, Lorazepam,Lorbamate, Lorcamide Hydrochloride, Loreclezole, Loreinadol, lorglumide,Lormetazepam, Lornoxicam, lornoxicam, Lortalamine, Lorzafone, losartan,Losartan potassium, losefamic Acid, loseric Acid, losigamone,losoxantrone, losulamide Meglumine, Losulazine Hydrochloride, losumeticAcid, lotasul, loteprednol, lotetric Acid, lothalamate Sodium,lothalamic Acid, lotrolan, lotroxic Acid, lovastatin, loversol,loviride, loxagiate Sodium, loxaglate Meglumine, loxaglic Acid,Loxapine, Loxoribine, loxotrizoic Acid, lubeluzole, LucanthoneHydrochloride, Lufironil, Lurosetron Mesylate, lurtotecan, lutetium,Lutrelin Acetate, luzindole, Lyapolate Sodium, Lycetamine, lydicamycin,Lydimycin, Lynestrenol, Lypressin, Lysine, lysofylline, lysostaphin,Maduramicin, Mafenide, magainin 2 amide, Magnesium Salicylate, MagnesiumSulfate, magnolol, maitansine, Malethamer, mallotoaponin,mallotochromene, Malotilate, malotilate, mangafodipir, manidipine,maniwamycin A, Mannitol, mannostatin A, manumycin E, manumycin F,mapinastine, Maprotiline, maraviroc, marimastat, Marinol, Masoprocol,maspin, massetolide, Maytansine, Mazapertine Succiniate, Mazindol,Mebendazole, Mebeverine Hydrochloride, Mebrofenin, Mebutamate,Mecamylamine Hydrochloride, Mechlorethamine Hydrochloride, meclizinehydrochloride, Meclocycline, Meclofenamate Sodium, Mecloqualone,Meclorisone Dibutyrate, Medazepam Hydrochloride, Medorinone,Medrogestone, Medroxalol, Medroxyprogesterone, Medrysone, MeelizineHydrochloride, Mefenamic Acid, Mefenidil, Mefenorex Hydrochloride,Mefexamide, Mefloquine Hydrochloride, Mefruside, Megalomicin PotassiumPhosphate, Megestrol Acetate, Meglumine, Meglutol, Melengestrol Acetate,Meloxicam, Melphalan, Memantine, Memotine Hydrochloride, MenabitanHydrochloride, Menoctone, menogaril, Menotropins, Meobentine Sulfate,Mepartricin, Mepenzolate Bromide, Meperidine Hydrochloride,Mephentermine Sulfate, Mephenyloin, Mephobarbital, MepivacaineHydrochloride, Meprobamate, Meptazinol Hydrochloride, Mequidox, MeraleinSodium, merbarone, Mercaptopurine, Mercufenol Chloride, Merisoprol,Meropenem, Mesalamine, Meseclazone, Mesoridazine, Mesterolone,Mestranol, Mesuprine Hydrochloride, Metalol Hydrochloride,Metaproterenol Polistirex, Metaraminol Bitartrate, Metaxalone,Meteneprost, meterelin, Metformin, Methacholine Chloride, Methacycline,methadone, Methadyl Acetate, Methalthiazide, MethamphetamineHydrochloride, Methaqualone, Methazolamide, Methdilazine, Methenamine,Methenolone Acetate, Methetoin, Methicillin Sodium, Methimazole,methioninase, Methionine, Methisazone, Methixene Hydrochloride,Methocarbamol, Methohexital Sodium, Methopholine, Methotrexate,Methotrimeprazine, methoxatone, methoxy polyethylene glycol-epoetinbeta, Methoxyflurane, Methsuximide, Methyclothiazide, MethylPalmoxirate, Methylatropine Nitrate, Methylbenzethonium Chloride,Methyldopa, Methyldopate Hydrochloride, Methylene Blue, MethylergonovineMaleate, methylhistamine, methylinosine monophosphate, Methylphenidate,Methylprednisolone, Methyltestosterone, Methynodiol Diacelate,Methysergide, Methysergide Maleate, Metiamide, Metiapine, Metioprim,metipamide, Metipranolol, Metizoline Hydrochloride, Metkephamid Acetate,metoclopramide, Metocurine Iodide, Metogest, Metolazone, Metopimazine,Metoprine, Metoprolol, Metoprolol tartrate, Metouizine, metrifonate,Metrizamide, Metrizoate Sodium, Metronidazole, Meturedepa, Metyrapone,Metyrosine, Mexiletine Hydrochloride, Mexrenoate Potassium, Mezlocillin,Mianserin Hydrochloride, mibefradil, Mibefradil Dihydrochloride,Mibolerone, michellamine B, Miconazole, microcolin A, Midaflur,Midazolam Hydrochloride, midodrine, mifepristone, Mifobate, miglitol,milacemide, milameline, mildronate, Milenperone, Milipertine,milnacipran, Milrinone, miltefosine, Mimbane Hydrochloride, minaprine,Minaxolone, Minocromil, Minocycline, Minocycline hydrochloride,Minoxidil, Mioflazine Hydrochloride, miokamycin, mipragoside,mirfentanil, mirimostim, Mirincamycin Hydrochloride, Mirisetron Maleate,Mirtazapine, Misonidazole, Misoprostol, Mitindomide, Mitocarcin,Mitocromin, Mitogillin, mitoguazone, mitolactol, Mitomalcin, Mitomycin,mitonafide, Mitosper, Mitotane, mitoxantrone, mivacurium chloride,mivazerol, mixanpril, Mixidine, mizolastine, mizoribine, Moclobemide,modafinil, Modaline Sulfate, Modecamide, moexipril, mofarotene,Mofegiline Hydrochloride, mofezolac, molgramostim, Molinazone, MolindoneHydrochloride, Molsidomine, mometasone, Monatepil Maleate, Monensin,Monoctanoin, montelukast, Montelukast Sodium, montirelin, mopidamol,moracizine, Morantel Tartrate, Moricizine, Morniflumate, Morphine,Morrhuate Sodium, mosapramine, mosapride, motilide, Motretinide,Moxalactam Disodium, Moxazocine, Moxifloxacin, moxiraprine, Moxnidazole,moxonidine, Mumps Skin Test Antigen, Muzolimine, mycaperoxide B,Mycophenolate mofetil, Mycophenolic Acid, myriaporone, Nabazenil,Nabilone, Nabitan Hydrochloride, Naboctate Hydrochloride, Nabumetone,N-acetyldinaline, Nadide, nadifloxacin, Nadolol, nadroparin calcium,nafadotride, nafamostat, nafarelin, Nafcillin Sodium, Nafenopin,Nafimidone Hydrochloride, Naflocort, Nafomine Malate, NafoxidineHydrochloride, Nafronyl Oxalate, Naftifine Hydrochloride, naftopidil,naglivan, nagrestip, Nalbuphine Hydrochloride, Nalidixate Sodium,Nalidixic Acid, nalmefene, Nalmexone Hydrochloride, naloxone,Naltrexone, Namoxyrate, Nandrolone Phenpropionate, NantradolHydrochloride, Napactadine Hydrochloride, napadisilate, NapamezoleHydrochloride, napaviin, Naphazoline Hydrochloride, naphterpin,Naproxen, Naproxen sodium, Naproxol, napsagatran, Naranol Hydrochloride,Narasin, naratriptan, nartograstim, nasaruplase, natalizumab, Natamycin,nateplase, Naxagolide Hydrochloride, Nebivolol, Nebramycin, nedaplatin,Nedocromil, Nefazodone Hydrochloride, Neflumozide Hydrochloride, NefopamHydrochloride, Nelezaprine Maleate, Nemazoline Hydrochloride,nemorubicin, Neomycin Palmitate, Neostigmine Bromide, neridronic acid,Netilmicin Sulfate, Neutramycin, Nevirapin Nexeridine Hydrochloride,Niacin, Nibroxane, Nicardipine Hydrochloride, Nicergoline, Niclosamide,Nicorandil, Nicotinamide, Nicotinyl Alcohol, Nifedipine, Nifirmerone,Nifluridide, Nifuradene, Nifuraldezone, Nifuratel, Nifuratrone,Nifurdazil, Nifurimide, Nifurpirinol, Nifurquinazol, Nifurthiazole,Nifurtimox, nilotinib, nilotinib hydrochloride monohydrate, nilutamide,Nilvadipine, Nimazone, Nimodipine, niperotidine, niravoline, Niridazole,nisamycin, Nisbuterol Mesylate, nisin, Nisobamate, Nisoldipine,Nisoxetin Nisterime Acetate, Nitarsone, nitazoxanide, nitecapone,Nitrafudam Hydrochloride, Nitralamine Hydrochloride, NitramisoleHydrochloride, Nitrazepam, Nitrendipine, Nitrocydine, Nitrodan,Nitrofurantoin, Nitrofurazone, Nitroglycerin, Nitromersol, Nitromide,Nitromifene Citrate, Nitrous Oxide, nitroxide antioxidant, nitrullyn,Nivazol, Nivimedone Sodium, Nizatidine, Noberastine, Nocodazole,Nogalamycin, Nolinium Bromide, Nomifensine Maleate, NoracymethadolHydrochloride, Norbolethone, Norepinephrine Bitartrate, Norethindrone,Norethynodrel, Norfurane, Norfloxacin, Norgestimate, Norgestomet,Norgestrel, Nortriptyline Hydrochloride, Noscapine, NovobiocinNylestriol, Nystatin, Obidoxime Chloride, Ocaperidone, OcfentanilHydrochloride, Ocinaplon, Octanoic Acid, Octazamide, OctenidineHydrochloride, Octodrine, Octreotide, Octriptyline Phosphate, Ofloxacin,Ofornine, okicenone, Olanzepine, Olmesartan, olmesartan medoxomil,olopatadine, olopatadine hydrochloride, olprinone, olsalazine,Olsalazine Sodium, Olvanil, Omalizumab, Omega-3 acid ethyl esters,omeprazole, onapristone, ondansetron, Ontazolast, Oocyte OpipramolHydrochloride, oracin, Orconazole Nitrate, Orgotein, Orlislat,Ormaplatin, Ormetoprim, Ornidazole, Orpanoxin, Orphenadrine Citrate,osaterone, Oseltamivir, otenzepad, Oxacillin Sodium, Oxagrelate,oxaliplatin, Oxamarin Hydrochloride, oxamisole, Oxamniquine,oxandrolone, Oxantel Pamoate, Oxaprotiline Hydrochloride, Oxaprozin,Oxarbazole, Oxatomide, oxaunomycin, Oxazepam, oxcarbazepine, Oxendolone,Oxethazaine, Oxetorone Fumarate, Oxfendazole, Oxfenicine, Oxibendazole,oxiconazole, Oxidopamine, Oxidronic Acid, Oxifungin Hydrochloride,Oxilorphan, Oximonam, Oximonam Sodium, Oxiperomide, oxiracetam,Oxiramide, Oxisuran, Oxmetidine Hydrochloride, oxodipine, OxogestonePhenopropionate, Oxolinic Acid, Oxprenolol Hydrochloride, Oxtriphylline,Oxybutynin Chloride, Oxychlorosene, Oxycodone, oxycodone hydrochloride,Oxymetazoline Hydrochloride, oxymetholone, Oxymorphone Hydrochloride,Oxypertine, Oxyphenbutazone, Oxypurinol, Oxytetracycline, Oxytocin,ozagrel, Ozlinone, Paclitaxel, palauamine, Paldimycin, palinavir,Palivizumab, palmitoylrhizoxin, Palmoxirate Sodium, pamaqueside,Pamatolol Sulfate, pamicogrel, Pamidronate Disodium, pamidronic acid,Panadiplon, panamesine, panaxytriol, Pancopride, Pancuronium Bromide,panipenem, pannorin, panomifene, pantethine, pantoprazole, PapaverineHydrochloride, parabactin, paracetamol, Parachlorophenol, Paraldehyde,Paramethasone Acetate, Paranyline Hydrochloride, Parapenzolate Bromide,Pararosaniline Pamoate, Parbendazole, Parconazole Hydrochloride,Paregoric, Pareptide Sulfate, Pargyline Hydrochloride, parnaparinsodium, Paromomycin Sulfate, Paroxetine, paroxetine hydrochloride,parthenolide, Partricin, Paulomycin, pazelliptine, Pazinaclone,Pazoxide, pazufloxacin, pefloxacin, pegaspargase, Pegorgotein, Pegylatedinterferon alfa-2a, Pelanserin Hydrochloride, peldesine,Peliomycipelretin, Pelrinone Hydrochloride, Pemedolac, Pemerid Nitrate,Pemetrexed, pemirolast, Pemoline, Penamecillin, Penbutolol Sulfate,Penciclovir, Penfluridol, Penicillamine, Penicillin G Benzathine,Penicillin G Potassium, Penicillin G Procaine, Penicillin G Sodium,Penicillin V Hydrabamine, Penicillin V Benzathine, Penicillin VPotassium, Pentabamate, Pentaerythritol Tetranitrate, pentafuside,pentamidine, pentamorphone, Pentamustine, Pentapiperium Methylsulfate,Pentazocine, Pentetic Acid, Pentiapine Maleate, pentigetide,Pentisomicin, Pentizidone Sodium, Pentobarbital, Pentomone, Pentopril,pentosan, pentostatin, Pentoxifylline, Pentrinitrol, pentrozole,Peplomycin Sulfate, Pepstatin, perflubron, perfofamide, Perfosfamide,pergolide, Perhexyline Maleate, perillyl alcohol, Perindopril,perindoprilat, Perlapin Permethrin, perospirone, Perphenazine,Phenacemide, phenaridine, phenazinomycin, Phenazopyridine Hydrochloride,Phenbutazone Sodium Glycerate, Phencarbamide, PhencyclidineHydrochloride, Phendimetrazine Tartrate, Phenelzine Sulfate, Phenformin,Phenmetrazine Hydrochloride, Phenobarbital, PhenoxybenzamineHydrochloride, Phenprocoumon, phenserine, phensuccinal, Phensuximide,Phentermine, Phentermine Hydrochloride, phentolamine mesilate,Phentoxifylline, Phenyl Aminosalicylate, phenylacetate, Phenylalanine,phenylalanylketoconazole, Phenylbutazone, Phenylephrine Hydrochloride,Phenylpropanolamine Hydrochloride, Phenylpropanolamine Polistirex,Phenyramidol Hydrochloride, Phenyloin, Phenyloin sodium, Physostigmine,picenadol, picibanil, Picotrin Diolamine, picroliv, picumeterol,pidotimod, Pifarnine, Pilocarpine, pilsicamide, pimagedine, PimetineHydrochloride, pimilprost, Pimobendan, Pimozide, Pinacidil, Pinadoline,Pindolol, pinnenol, pinocebrin, Pinoxepin Hydrochloride, pioglitazone,Pipamperone, Pipazethate, pipecuronium bromide, Piperacetazine,Piperacillin, Piperacillin Sodium, Piperamide Maleate, piperazinc,Pipobroman, Piposulfan, Pipotiazine Palmitate, Pipoxolan Hydrochloride,Piprozolin, Piquindone Hydrochloride, Piquizil Hydrochloride, Piracetam,Pirandamine Hydrochloride, pirarubicin, Pirazmonam Sodium, Pirazolac,Pirbenicillin Sodium, Pirbuterol Acetate, Pirenperone, PirenzepineHydrochloride, piretanide, Pirfenidone, Piridicillin Sodium, PiridronateSodium, Piriprost, piritrexim, Pirlimycin Hydrochloride, pirlindole,pirmagrel, Pirmenol Hydrochloride, Pirnabine, Piroctone, Pirodavir,pirodomast, Pirogliride Tartrate, Pirolate, Pirolazamide, PiroxantroneHydrochloride, Piroxicam, Piroximone, Pirprofen, Pirquinozol,Pirsidomine, Pivampicillin Hydrochloride, Pivopril, Pizotyline, placetinA, Plicamycin, Plomestane, Pobilukast Edamine, Podofilox, PoisonoakExtract, Poldine Methylsulfate, Poliglusam, Polignate Sodium, PolymyxinB Sulfate, Polythiazide, Ponalrestat, Porfimer Sodium, Porfiromycin,Potassium Chloride, Potassium Iodide, Potassium Permanganate,Povidone-Iodine, Practolol, Pralidoxime Chloride, Pramipexole,Pramiracetam Hydrochloride, Pramoxine Hydrochloride, Pranolium Chloride,Pravadoline Maleate, Pravastatin, Pravastatin sodium, Prazepam,Prazosin, Prazosin Hydrochloride, Prednazate, Prednicarbate,Prednimustine, Prednisolone, prednisolone quetiapine fumerate,Prednisone, Prednival, Pregabalin, Pregnenolone Succiniate, PrenalterolHydrochloride, Prenylamine, Pridefine Hydrochloride, Prifelone,Prilocalne Hydrochloride, Prilosec, Primaquine Phosphate, Primidolol,Primidone, Prinivil, Prinomide Tromethamine, Prinoxodan,pritosufloxacin, Prizidilol Hydrochloride, Proadifen Hydrochloride,Probenecid, Probicromil Calcium, Probucol, Procainamide Hydrochloride,Procaine Hydrochloride, Procarbazine Hydrochloride, ProcaterolHydrochloride, Prochlorperazine, Procinonide, Proclonol, ProcyclidineHydrochloride, Prodilidine Hydrochloride, Prodolic Acid, ProfadolHydrochloride, Progabide, Progesterone, Proglumide, Proinsulin (human),Proline, Prolintane Hydrochloride, Promazine Hydrochloride,Promethazine, Promethazine hydrochloride, Propafenone Hydrochloride,propagermanium, Propanidid, Propantheline Bromide, ProparacaineHydrochloride, Propatyl Nitrate, propentofylline, PropenzolateHydrochloride, Propikacin, Propiomazine, Propionic Acid,propionylcarnitine, propiram, propiram, propiverine, Propofol,Proponolol hydrochloride, Propoxycaine Hydrochloride, PropoxypheneHydrochloride, Propranolol Hydrochloride, Propulsid, propylbis-acridone,Propylhexedrine, Propyliodone, Propylthiouracil, Proquazone, ProrenoatePotassium, Proroxan Hydrochloride, Proscillaridin, Prostalene,prostratin, Protamine Sulfate, protegrin, Protirelin, ProtriptylineHydrochloride, Proxazole, Proxazole Citrate, Proxicromil, ProxorphanTartrate, prulifloxacin, pseudoephedrine, Pseudophedrine hydrochloride,Puromycin, Pyrabrom, Pyrantel Pamoate, Pyrazinamide, Pyrazofurin,pyrazoloacridine, Pyridostigmine Bromide, Pyridoxine hydrochloride,Pyrilamine Maleate, Pyrimethamine, Pyrinoline, Pyrithione Sodium,Pyrithione Zinc, Pyrovalerone Hydrochloride, Pyroxamine Maleate,Pyrrocaine, Pyrroliphene Hydrochloride, Pyrrolnitrin, Pyrvinium Pamoate,Quadazocine Mesylate, Quazepam, Quazinone, Quazodine, Quazolast,quetiapine, quetiapine fumarate, quiflapon, quinagolide, QuinaldineBlue, quinapril, Quinapril hydrochloride, Quinazosin Hydrochloride,Quinbolone, Quinctolate, Quindecamine Acetate, Quindonium Bromide,Quinelorane Hydrochloride, Quinestrol, Quinfamide, Quingestanol Acetate,Quingestrone, Quinidine Gluconate, Quinielorane Hydrochloride, QuinineSulfate, Quinpirole Hydrochloride, Quinterenol Sulfate, QuinucliumBromide, Quinupristin, Quipazine Maleate, Rabeprazole, RabeprazoleSodium, Racephenicol, Racepinephrine, Rafoxanide, Ralitoline,raloxifene, raltegravir, raltitrexed, ramatroban, Ramipril, Ramoplanin,ramosetron, ranelic acid, Ranimycin, Ranitidine, Ranitidinehydrochloride, ranolazine, Rauwolfia Serpentina, recainam, RecainamHydrochloride, Reclazepam, Recombinant factor VIII, regavirumab,Regramostim, Relaxin, Relomycin, Remacemide Hydrochloride, RemifentanilHydrochloride, Remiprostol, Remoxipride, Repirinast, Repromicin,Reproterol Hydrochloride, Reserpine, resinferatoxin, Resorcinol,retapamulin, retelliptine demethylated, reticulon, reviparin sodium,revizinone, rhenium etidronate, rhizoxin, RI retinamide, Ribaminol,Ribavirin, Riboprine, ricasetron, Ridogrel, Rifabutin, Rifametane,Rifamexil, Rifamide, Rifampin, Rifapentine, Rifaximin, rilopirox,Riluzole, rimantadine, Rimcazole Hydrochloride, Rimexolone, RimiterolHydrobromide, Rimonabant, rimoprogin, riodipine, Rioprostil, Ripazepam,ripisartan, Risedronate, Risedronate Sodium, risedronic acid, Risocaine,Risotilide Hydrochloride, rispenzepine, Risperdal, Risperidone,Ritanserin, ritipenem, Ritodrine, Ritolukast, ritonavir, rituximab,rivastigmine, rivastigmine tartrate, Rizatriptan, rizatriptan benzoate,Rocastine Hydrochloride, Rocuronium Bromide, Rodocaine, Roflurane,Rogletimide, rohitukine, rokitamycin, Roletamicide, Rolgamidine,Rolicyprine, Rolipram, Rolitetracycline, Rolodine, Romazarit, romurtide,Ronidazole, Ropinirole, Ropitoin Hydrochloride, ropivacaine, Ropizine,roquinimex, Rosaramicin, rosiglitazone, Rosiglitazone maleate,Rosoxacin, Rosuvastatin, Rotavirus vaccine, rotigotine, Rotoxamine,roxaitidine, Roxarsone, roxindole, roxithromycin, rubiginone B1,ruboxyl, rufloxacin, rupatidine, Rutamycin, ruzadolane, Sabeluzole,safingol, safironil, saintopin, salbutamol, Salbutamol sulfate,Salcolex, Salethamide Maleate, Salicyl Alcohol, Salicylamide, SalicylateMeglumine, Salicylic Acid, Salmeterol, Salnacediin, Salsalate,sameridine, sampatrilat, Sancycline, sanfetrinem, Sanguinarium Chloride,Saperconazole, saprisartan, sapropterin, sapropterin dihydrochloride,saquinavir, Sarafloxacin Hydrochloride, Saralasin Acetate, sarcophytolA, sargramostim, Sarmoxicillin, Sarpicillin, sarpogrelate, saruplase,saterinone, satigrel, satumomab pendetide, Scopafungin, ScopolamineHydrobromide, Scrazaipine Hydrochloride, Secalciferol, Secobarbital,Seelzone, segiline, Seglitide Acetate, Selegiline Hydrochloride,Selenium Sulfide, Selenomethionine Se-75, Selfotel, sematilide,semduramicin, semotiadil, semustine, Sepazonium Chloride, SeperidolHydrochloride, Seprilose, Seproxetine Hydrochloride, Seractide Acetate,Sergolexole Maleate, Serine, Sermetacin, Sermorelin Acetate,sertaconazole, sertindole, sertraline, sertraline hydrochloride,S-ethynyluracil, setiptiline, Setoperone, Sevelamer, sevirumab,sevoflurane, sezolamide, Sibopirdine, Sibutramine Hydrochloride,Silandrone, Sildenafil, sildenafil citrate, silipide, silteplase, SilverNitrate, simendan, Simtrazene, Simvastatin, Sincalide, Sinefungin,sinitrodil, sinnabidol, sipatrigine, sirolimus, Sisomicin, Sitagliptin,Sitogluside, sizofuran, sobuzoxane, Sodium Amylosulfate, Sodium IodideI-123, Sodium Nitroprusside, Sodium Oxybate, sodium phenylacetate,Sodium Salicylate, Sodium valproate, Solifenacin, solverol, SolypertineTartrate, Somalapor, Somantadine Hydrochloride, somatomedin B,somatomedin C, Somatostatin, somatrem, somatropin, Somenopor,Somidobove, Sorbinil, Sorivudine, sotalol, Soterenol Hydrochloride,Sparfioxacin, Sparfosate Sodium, sparfosic acid, Sparsomy, SparteineSulfate, Spectinomycin Hydrochloride, spicamycin D, Spiperone,Spiradoline Mesylate, Spiramycin, Spirapril Hydrochloride, Spiraprilat,Spirogermanium Hydrochloride, Spiromustine, Spironolactone, Spiroplatin,Spiroxasone, splenopentin, spongistatin, Sprodiamide, squalamine,Stallimycin Hydrochloride, Stannous Pyrophosphate, Stannous SulfurColloid, Stanozolol, Statolon, staurosporine, stavudine, Steffimycin,Stenbolone Acetate, stepronin, Stilbazium Iodide, Stilonium Iodide,stipiamide, Stiripentol, stobadine, Streptomycin Sulfate,Streptonicozid, Streptonigrin, Streptozocin, Strontium Chloride Sr-89,succibun, Succimer, Succinylcholine Chloride, Sucralfate, SucrosofatePotassium, Sudoxicam, Sufentanil, Sufotidine, Sulazepam, SulbactamPivoxil, Sulconazole Nitrate, Sulfabenz, Sulfabenzamide, Sulfacetamide,Sulfacytine, Sulfadiazine, Sulfadoxine, Sulfalene, Sulfamerazine,Sulfameter, Sulfamethazine, Sulfamethizole, Sulfamethoxazole,Sulfamonomethoxine, Sulfamoxole, Sulfanilate Zinc, Sulfanitran,sulfasalazine, Sulfasomizole, Sulfazamet, Sulfinalol Hydrochloride,sulfinosine, Sulfinpyrazone, Sulfisoxazole, Sulfomethoxazole,Sulfomyxin, Sulfonterol Hydrochloride, sulfoxamine, Sulinldac, Sulmarin,Sulnidazole, Suloctidil, Sulofenur, sulopenem, Suloxifen Oxalate,Sulpiride, Sulprostone, sultamicillin, Sulthiame, sultopride, sulukast,Sumarotene, sumatriptan, Sumatriptan succinate, Suncillin Sodium,Suproclone, Suprofen, suradista, suramin, Surfomer, Suricamide Maleate,Suritozole, Suronacrine Maleate, Suxemerid Sulfate, swainsonine,symakalim, Symclosene, Symetine Hydrochloride, Taciamine Hydrochloride,Tacrine Hydrochloride, Tacrolimus, Tadalafil, TalampicillinHydrochloride, Taleranol, Talisomycin, tallimustine, Talmetacin,Talniflumate, Talopram Hydrochloride, Talosalate, TametralineHydrochloride, Tamoxifen, tamoxifen citrate, Tampramine Fumarate,Tamsulosin, Tamsulosin Hydrochloride, Tandamine Hydrochloride,tandospirone, tapgen, taprostene, Tasosartan, tauromustine, Taxane,Taxoid, Tazadolene Succinate, tazanolast, tazarotene, TazifyllineHydrochloride, Tazobactam, Tazofelone, Tazolol Hydrochloride,Tebufelone, Tebuquine, Teclozan, Tecogalan Sodium, Teecleukin,Teflurane, Tegafur, Tegaserod, Tegretol, Teicoplanin, telenzepine,tellurapyrylium, telmesteine, telmisartan, Teloxantrone Hydrochloride,Teludipine Hydrochloride, Temafloxacin Hydrochloride, Tematropium Methylsulfate, Temazepam, Temelastine, temocapril, Temocillin, temoporfin,temozolomide, temsirolimus, Tenidap, Teniposide, Tenofovir, tenosal,tenoxicam, tepirindole, Tepoxalin, Teprotide, terazosin, TerazosinHydrochloride, Terbinafine, Terbutaline Sulfate, Terconazole,terfenadine, terfiavoxate, terguride, Teriparatide, TeriparatideAcetate, terlakiren, terlipressin, terodiline, Teroxalene Hydrochloride,Teroxirone, tertatolol, Tesicam, Tesimide, Testolactone, Testosterone,Tetracaine, tetrachlorodecaoxide, Tetracycline, Tetracyclinehydrochloride, Tetrahydrozoline Hydrochloride, TetramisoleHydrochloride, Tetrazolast Meglumine, tetrazomine, Tetrofosmin,Tetroquinone, Tetroxoprim, Tetrydamine, thaliblastine, Thalidomide,Theofibrate, Theophylline, Thiabendazole, Thiamiprine, Thiamphenicol,Thiamylal, Thiazesim Hydrochloride, Thiazinamium Chloride,Thiethylperazine, Thiithixene, Thimerfonate Sodium, Thimerosal,thiocoraline, thiofedrine, Thioguanine, thiomarinol, Thiopental Sodium,thioperamide, Thioridazine, Thiotepa, Thiphenamil Hydrochloride,Thiphencillin Potassium, Thiram, Thozalinone, Threonine, Thrombin,thrombopoietin, thymalfasin, thymopentin, thymotrinan, ThyromedanHydrochloride, Thyroxine, Tiacrilast, Tiacrilast Sodium, tiagabine,Tiamenidine, tianeptine, tiapafant, Tiapamil Hydrochloride, TiaramideHydrochloride, Tiazofurin, Tibenelast Sodium, Tibolone, Tibric Acid,Ticabesone Propionate, Ticarbodine, Ticarcillin Cresyl Sodium,Ticlatone, ticlopidine, Ticrynafen, tienoxolol, Tifurac Sodium,Tigemonam Dicholine, Tigestol, Tiletamine Hydrochloride, TilidineHydrochloride, tilisolol, tilnoprofenarbamel, Tilorone Hydrochloride,Tiludronate Disodium, tiludronic acid, Timefurone, Timobesone Acetate,Timolol, Timolol meleate, Tinabinol, Timidazole, Tinzaparin Sodium,Tioconazole, Tiodazosin, Tiodonium Chloride, Tioperidone Hydrochloride,Tiopinac, Tiospirone Hydrochloride, Tiotidine, Tiotropium, tiotropiumbromide, Tioxidazole, Tipentosin Hydrochloride, tipranavir, Tipredane,Tiprenolol Hydrochloride, Tiprinast Meglumine, Tipropidil Hydrochloride,Tiqueside, Tiquinamide Hydrochloride, tirandalydigin, Tirapazamine,tirilazad, tirofiban, tiropramide, titanocene dichloride, Tixanox,Tixocortol Pivalate, Tizanidine Hydrochloride, TnmethobenzamideHydrochloride, Tobramycin, Tocamide, Tocamphyl, Tofenacin Hydrochloride,Tolamolol, Tolazamide, Tolazoline Hydrochloride, Tolbutamide, Tolcapone,Tolciclate, Tolfamide, Tolgabide, Tolimidone, Tolindate, Tolmetin,Tolnaftate, Tolpovidone, Tolpyrramide, Tolrestat, Tolterodine,tolterodine tartrate, Tomelukast, Tomoxetine Hydrochloride, TonazocineMesylate, Topiramate, topotecan, Topotecan Hydrochloride, topsentin,Topterone, Toquizine, torasemide, toremifene, Torsemide, Tosifen,Tosufloxacin, totipotent stem cell factor (TSCF), Tracazolate,trafermin, Tralonide, Tramadol, Tramadol Hydrochloride, TramazolineHydrochloride, trandolapril, Tranexamic Acid, Tranilast, Transcamide,trastuzumab, traxanox, Trazodone Hydrochloride, TrebenzomineHydrochloride, Trefentanil Hydrochloride, Treloxinate, Trepipam Maleate,Trestolone Acetate, tretinoin, Triacetin, triacetyluridine, Triafungin,Triamcinolone, Triampyzine Sulfate, Triamterene, Triazolam, Tribenoside,tricaprilin, Tricetamide, Trichlormethiazide, trichohyalin, triciribine,Tricitrates, Triclofenol piperazine, Triclofos Sodium, trientine,Trifenagrel, triflavin, Triflocin, Triflubazam, Triflumidate,Trifluoperazine Hydrochloride, Trifluperidol, Triflupromazine,Triflupromazine Hydrochloride, Trifluridine, TrihexyphenidylHydrochloride, Trilostane, Trimazosin Hydrochloride, trimegestone,Trimeprazine Tartrate, Trimethadione, Trimethaphan Camsylate,Trimethoprim, Trimetozine, Trimetrexate, Trimipramine, Trimoprostil,Trimoxamine Hydrochloride, Triolein, Trioxifene Mesylate, Tripamide,Tripelennamine Hydrochloride, Triprolidine Hydrochloride, Triptorelin,Trisulfapyrimidines, Troclosene Potassium, troglitazone, Trolamine,Troleandomycin, trombodipine, trometamol, Tropanserin Hydrochloride,Tropicamide, tropine, tropisetron, trospectomycin, trovafloxacin,trovirdine, Tryptophan, Tuberculin, Tubocurarine Chloride, TubulozoleHydrochloride, tucarcsol, tulobuterol, turosteride, Tybamate, tylogenin,Tyropanoate Sodium, Tyrosine, Tyrothricin, tyrphostins, ubenimex,Uldazepam, Undecylenic Acid, Uracil Mustard, urapidil, Urea, Uredepa,uridine triphosphate, Urofollitropin, Urokinase, Ursodiol, valaciclovir,Valacyclovir hydrochloride, Valine, Valnoctamide, Valproate semisodium,Valproic Acid, valsartan, vamicamide, vanadeine, Vancomycin, vaminolol,Vapiprost Hydrochloride, Vapreotide, Vardenafil, Varenicline, variolinB, Vasopressin, Vecuronium Bromide, velaresol, Velnacrine Maleate,venlafaxine, Venlafaxine hydrochloride, Veradoline Hydrochloride,veramine, Verapamil Hydrochloride, verdins, Verilopam Hydrochloride,Verlukast, Verofylline, veroxan, verteporfin, Vesnarinone, vexibinol,Vidarabine, vigabatrin, vildagliptin, Viloxazine Hydrochloride,Vinblastine Sulfate, vinburnine citrate, Vincofos, vinconate,Vincristine Sulfate, Vindesine, Vindesine Sulfate, Vinepidine Sulfate,Vinglycinate Sulfate, Vinleurosine Sulfate, vinorelbine, vinpocetine,vintoperol, vinxaltine, Vinzolidine Sulfate, Viprostol, Virginiamycin,Viridofulvin, Viroxime, vitaxin, Voglibose, Volazocine, voriconazole,vorozole, voxergolide, Wafarin, Xamoterol, Xanomeline, Xanoxate Sodium,Xanthinol Niacinate, xemiloflban, Xenalipin, Xenbucin, Xilobam,ximoprofen, Xipamide, Xorphanol Mesylate, Xylamidine Tosylate, XylazineHydrochloride, Xylometazoline Hydrochloride, xylose, yangambin,zabicipril, zacopride, zafirlukast, Zalcitabine, Zaleplon, zalospirone,Zaltidine Hydrochloride, zaltoprofen, zanamivir, zankiren, zanoterone,Zantac, Zarirlukast, zatebradine, zatosetron, Zatosetron Maleate,zenarestat, Zenazocine Mesylate, Zeniplatin, Zeranol, Zidometacin,Zidovudine, zifrosilone, Zilantel, zilascorb, zileuton, ZimeldineHydrochloride, Zinc Undecylenate, Zindotrine, ZinoconazoleHydrochloride, Zinostatin, Zinterol Hydrochloride, Zinviroxime,ziprasidone, Zobolt, Zofenopril Calcium, Zofenoprilat, ZolamineHydrochloride, Zolazepam Hydrochloride, Zoledronate, ZolertineHydrochloride, zolmitriptan, zolpidem, Zomepirac Sodium, Zometapine,Zoniclezole Hydrochloride, Zonisamide, zopiclone, Zopolrestat,Zorbamyciin, Zorubicin Hydrochloride, zotepine, Zucapsaicin, andpharmaceutically acceptable salts thereof.

REFERENCES

The following references are incorporated herein by reference:

-   The Journal of Urology, Vol. 160, 1572-1575, October 1998; Sato    “Restoration of Sexual Behavior and Dopaminergic Neurotransmission    by Long Term Exogenous Testosterone Replacement in Male Rats.”-   Yonago Acta medica 2005; 48:93-99; S. Morizane “Effects of    Testosterone Replacement on Lower Urinary Tract Functions in Elderly    Male Rats.”-   U.S. Patent Publication 20100152699-   WIPO Patent Publication WO/2011/146699

1. A device for administering a therapeutic agent, the devicecomprising: an implantable device comprising a reservoir; a channeledmember in fluid communication with the reservoir; and a compoundcomprising the therapeutic agent and a solubilizer disposed within thereservoir and in fluid communication with the channeled member.
 2. Thedevice of claim 1 wherein the compound comprises a testosterone ether,ester, or salt.
 3. The device of claim 1 wherein the compound comprisestestosterone enanthate.
 4. The device of claim 1 wherein the compoundcomprises testosterone cypionate.
 5. The device of claim 1 wherein thecompound comprises testosterone propionate.
 6. The device of claim 1wherein the compound comprises methyltestosterone.
 7. The device ofclaim 1 wherein the solubilizer comprises an oil.
 8. The device of claim1 wherein the solubilizer comprises at least one of: Gelucire 44/14,Gelucire 50/13, Peceol, Labrafil M2125 CS, Labrafil M1944 CS, Labrasol,Tween 80, Crodasol, Brij 30, Glycerox 767, NOVOL (Oleyl Alcohol), ETOCAS(PEG-35 Castor Oil), Arlosolve (Dimethyl lsosobride), PEG300, Maisine35-1, Transcutol HP, Glycerin, Span 80, Span 85, Compritol 888,Propylene Glycol, Dibutyl Sebacate, Triacetin, Miglyol 810, Miglyol 812,Myvacet, Softigen 701, Softigen 767, Kolliphor HS15, Kolliphor RH40,Kolliphor ELP, Stearic Acid, Cetyl Palmitate, Lauroglycol 90,Lauroglycol FCC, Labrafac PG, Labrafac Lipophile WL 1349, Miranol,soybean oil, corn oil, olive oil, castor oil, sesame oil, light mineraloil, heavy mineral oil, coconut oil, canola oil, dimethyl sulfoxide(DMSO), N-Methylpyrrolidone (NMP), Benzyl Benzoate, Capryol PGMC,Glyceryl Monostearate, Vitamin E TPGS and Benzyl Alcohol.
 9. The deviceof claim 1 wherein the channeled member comprises a nanochannel.
 10. Thedevice of claim 9 wherein the nanochannel has a dimension of up to 50nm.
 11. The device of claim 9 wherein the nanochannel has a dimension inthe range of 50-100 nm.
 12. The device of claim 9 wherein thenanochannel has a dimension in the range of 100-150 nm.
 13. The deviceof claim 9 wherein the nanochannel has a dimension in the range of150-170 nm.
 14. The device of claim 9 wherein the nanochannel has adimension in the range of 170-190 nm.
 15. The device of claim 9 whereinthe nanochannel has a dimension in the range of 190-210 nm.
 16. Thedevice of claim 9 wherein the nanochannel has a dimension in the rangeof 210-225 nm.
 17. The device of claim 9 wherein the nanochannel has adimension in the range of 225-240 nm.
 18. The device of claim 9 whereinthe nanochannel has a dimension in the range of 240-250 nm.
 19. Thedevice of claim 1 wherein the channeled member comprises microchannels.20. The device of claim 1 wherein the device comprises an injectionport.
 21. The device of claim 1 wherein the device comprises a vent. 22.A method of administering a therapeutic agent, the method comprising:inserting a device into an area of a human and or animal anatomy,wherein the device comprises: a reservoir; a channeled member in fluidcommunication with the reservoir; and a compound comprising thetherapeutic agent and a solubilizer disposed within the reservoir and influid communication with the channeled member; and releasing at least aportion of the therapeutic agent from the device into the area of thehuman anatomy.
 23. The method of claim 22 wherein the device isconfigured to release the therapeutic agent at a substantially constantrelease rate for a dosage period of at least one week.
 24. The method ofclaim 22 wherein the device is configured to release the therapeuticagent at a substantially constant release rate for a dosage period of atleast one month.
 25. The method of claim 22 wherein the device isconfigured to release the therapeutic agent at a substantially constantrelease rate for a dosage period of at least six months.
 26. The methodof claim 22 wherein the device is configured to release the therapeuticagent at a substantially constant release rate for a dosage period of atleast one year.
 27. The method of claim 22 wherein the compoundcomprises a testosterone ether, ester, or salt.
 28. The method of claim22 wherein the compound comprises testosterone enanthate.
 29. The methodof claim 22 wherein the compound comprises testosterone cypionate. 30.The method of claim 22 wherein the compound comprises testosteronepropionate.
 31. The method of claim 22 wherein the compound comprisesmethyltestosterone.
 32. The method of claim 22 wherein the solubilizercomprises an oil.
 33. The method of claim 22 wherein the solubilizercomprises at least one of: Gelucire 44/14, Gelucire 50/13, Peceol,Labrafil M2125 CS, Labrafil M1944 CS, Labrasol, Tween 80, Crodasol, Brij30, Glycerox 767, NOVOL (Oleyl Alcohol), ETOCAS (PEG-35 Castor Oil),Arlosolve (Dimethyl lsosobride), PEG300, Maisine 35-1, Transcutol HP,Glycerin, Span 80, Span 85, Compritol 888, Propylene Glycol, DibutylSebacate, Triacetin, Miglyol 810, Miglyol 812, Myvacet, Softigen 701,Softigen 767, Kolliphor HS15, Kolliphor RH40, Kolliphor ELP, StearicAcid, Cetyl Palmitate, Lauroglycol 90, Lauroglycol FCC, Labrafac PG,Labrafac Lipophile WL 1349, Miranol, soybean oil, corn oil, olive oil,castor oil, sesame oil, light mineral oil, heavy mineral oil, coconutoil, canola oil, dimethyl sulfoxide (DMSO), N-Methylpyrrolidone (NMP),Benzyl Benzoate, Capryol PGMC, Glyceryl Monostearate, Vitamin E TPGS andBenzyl Alcohol.
 34. The method of claim 22 wherein the channeled membercomprises a nanochannel.
 35. The device of claim 34 wherein thenanochannel has a dimension in the range of 50-100 nm.
 36. The device ofclaim 34 wherein the nanochannel has a dimension in the range of 100-150nm.
 37. The device of claim 34 wherein the nanochannel has a dimensionin the range of 150-170 nm.
 38. The device of claim 34 wherein thenanochannel has a dimension in the range of 170-190 nm.
 39. The deviceof claim 34 wherein the nanochannel has a dimension in the range of190-210 nm.
 40. The device of claim 34 wherein the nanochannel has adimension in the range of 210-225 nm.
 41. The device of claim 34 whereinthe nanochannel has a dimension in the range of 225-240 nm.
 42. Thedevice of claim 34 wherein the nanochannel has a dimension in the rangeof 240-250 nm
 43. The method of claim 22 wherein the channeled membercomprises microchannels.
 44. The method of claim 22 wherein the devicecomprises an injection port.
 45. The method of claim 22 wherein thedevice comprises a vent.